用于诱导组织再生的肽及其应用

文档序号:1651927 发布日期:2019-12-24 浏览:27次 >En<

阅读说明:本技术 用于诱导组织再生的肽及其应用 (Peptides for inducing tissue regeneration and uses thereof ) 是由 二桥阳一郎 河内智行 山津维子 麓昌高 山崎尊彦 于 2018-04-24 设计创作,主要内容包括:本发明提供可用作下述组合物的有效成分的肽:用于刺激PDGFRα阳性细胞迁移的组合物、用于将骨髓间充质干细胞从骨髄募集到外周血中的组合物、用于使组织再生的组合物、或者用于刺激骨髄来源的基质细胞迁移的组合物。(The present invention provides peptides useful as active ingredients of the following compositions: a composition for stimulating the migration of PDGFR α -positive cells, a composition for recruiting bone marrow mesenchymal stem cells from the bone marrow into the peripheral blood, a composition for regenerating tissue, or a composition for stimulating the migration of bone marrow derived matrix cells.)

用于诱导组织再生的肽及其应用

技术领域

本发明涉及用于诱导组织再生的肽及其应用。

背景技术

在生物体内的各脏器(器官)、组织中存在着维持其结构或功能的稳态的组织干细胞,这正为人们所明确。例如,心脏中存在心肌干细胞、脑中存在神经干细胞、皮肤中存在表皮干细胞或毛囊干细胞,这些干细胞毕生供给心肌细胞、神经细胞、表皮细胞或毛囊上皮细胞以维持心脏、脑、皮肤的结构/功能。另一方面,骨髄中存在分化成红细胞、白细胞、血小板等血液细胞的造血干细胞。

这些来自造血干细胞的血液细胞通过血流在体内的所有脏器或组织中循环,对供氧、免疫反应、止血/损伤组织修复等生命维持发挥着不可或缺的功能。即,与其说骨髄造血干细胞维持其局部存在的组织即骨髄或骨组织的稳态,不如说其通过外周循环有助于维持生物体内所有组织的稳态。

近年来,虽然明确了骨髄内除了造血干细胞以外还存在着可分化成骨、软骨、脂肪等中胚层组织、进一步分化成神经或表皮等外胚层组织的间充质干细胞,但其在生物体内的存在意义尚有许多不明之处。然而,如果骨髄内存在着通过外周循环供给血液细胞来维持所有的组织、脏器的稳态的造血干细胞,则可预料以下的可能性:同样存在于骨髄内的间充质干细胞也通过外周循环向必需的生物体内组织/脏器提供可分化成骨、软骨、脂肪、神经、上皮等的细胞,从而有助于维持生物体组织的稳态。

目前,正在大力地开发下述的再生医疗:通过采集骨髄血(骨髄)来采集骨髓间充质干细胞,通过细胞培养使其增殖后,移植到顽固性组织损伤部位或者外周循环血中,以诱导损伤组织的再生。已经在脑梗塞(脑梗死)、心肌梗塞(心肌梗死)、顽固性皮肤溃疡等的再生医疗中推行骨髓间充质干细胞移植的临床应用。而且,已明确所移植的骨髓间充质干细胞在生物体内局部发挥炎症/免疫反应抑制作用、纤维性瘢痕形成抑制作用,作为针对骨髄移植或输血后的严重副作用即移植物抗宿主病(graft versus host disease, GVHD)或作为自身免疫性疾病的硬皮病的新的治疗方法,骨髓间充质干细胞移植疗法的临床试验已开始进行。然而,含有骨髓间充质干细胞的骨髄血只能通过向髂骨内多次刺入粗针的开放性技术(観血的手法)进行采集。另外,若骨髓间充质干细胞在体外持续进行继代培养,则会逐渐失去增殖能力或多分化能力。而且,由于基于保证生物体内移植安全性的高质量管理的骨髓间充质干细胞培养需要CPC(cell processing center,细胞处理中心)等特殊培养设备,所以目前仅能在非常有限的大学或企业实施。即,为了向正为顽固性组织损伤而苦恼的全世界许多患者提供使用骨髓间充质干细胞的再生医疗,用于可在所有医疗设施中实施的间充质干细胞再生医疗的技术开发成为紧迫的课题。

HMGB1(High mobility group box 1:高迁移率族蛋白1)在约30年前被鉴定为非组蛋白染色质蛋白,其控制核内染色质结构从而控制基因表达或DNA修复。HMGB1蛋白的结构主要由两个DNA结合结构域构成,位于N末端侧的DNA结合结构域称为A-box,C末端侧的DNA结合结构域称为B-box。根据以往的研究明确了:在HMGB1分子内与TLR结合而引发炎症反应的结构域存在于B-box内。

据报道,在小鼠中制作皮肤溃疡或脑梗塞后从尾静脉给予重组HMGB1蛋白,从而将PDGFRα阳性细胞从骨髄募集(動員)到血中,进一步集聚在皮肤溃疡部或脑梗塞部,强烈诱导皮肤溃疡或脑梗塞的再生。已经报道了骨髄内PDGFRα阳性细胞是可分化成骨、软骨、脂肪、还可分化成神经或上皮的间充质干细胞。即,通过给予HMGB1将骨髄内PDGFRα阳性间充质干细胞募集到外周循环中,从而无需将其取出到体外进行特殊培养,即可使多数的间充质干细胞在生物体内集聚于损伤组织。

通过开发HMGB1作为基于生物体内骨髓间充质干细胞血中募集的损伤组织再生诱导药物,使得可在所有医疗机构实施基于骨髓间充质干细胞的再生诱导医疗。其结果,可解决使用骨髓间充质干细胞的上述的目前再生医疗所面临的许多课题。

如上所述,HMGB1药物是促进骨髓间充质干细胞向血中募集、向损伤组织集聚、并诱导体内的组织再生的划时代的治疗药。关于HMGB1已经报道了:不仅是HMGB1全长蛋白就连HMGB1蛋白的片段也具有同样的作用。

现有技术文献

专利文献

专利文献1:WO2008/053892;

专利文献2:WO2007/015546;

专利文献3:WO2009/133939;

专利文献4:WO2009/133943;

专利文献5:WO2009/133940;

专利文献6:日本特表2005-537253;

专利文献7:WO2012/147470;

非专利文献

非专利文献1:Bustin等人, Mol Cell Biol, 19:5237-5246, 1999年;

非专利文献2:Hori等人, J. Biol. Chem., 270, 25752-25761, 1995年;

非专利文献3:Wang等人, Science, 285: 248-251, 1999年;

非专利文献4:Muller等人, EMBO J, 20: 4337-4340, 2001年;

非专利文献5:Wang等人, Science, 285: 248-251, 1999年;

非专利文献6:Germani等人, J Leukoc Biol. Jan; 81(1): 41-5, 2007年;

非专利文献7:Palumbo等人, J. Cell Biol., 164: 441-449, 2004年;

非专利文献8:Merenmies等人, J. Biol. Chem., 266: 16722-16729, 1991年;

非专利文献9:Wu Y等人, Stem cells, 25:2648-2659, 2007年;

非专利文献10:Tamai等人, Proc Natl Acad Sci U S A. 2011 Apr 4. [Epub aheadof print], 108: 6609-6614, 2011年;

非专利文献11:Yang等人, J Leukoc Biol. Jan; 81(1): 59-66, 2007年。

发明内容

发明所要解决的课题

本发明所要解決的课题在于:提供具有骨髄来源的基质细胞的迁移活性的肽、即用于诱导组织再生的肽。

用于解决课题的手段

本发明人深入研究的结果发现了:在由HMGB1蛋白的第1~44位的氨基酸构成的肽中在第43位和/或第44位进行了氨基酸取代的肽、以及在由该HMGB1蛋白的第2~44位的氨基酸构成的肽中在第43位和/或第44位进行了氨基酸取代的肽,具有小鼠骨髄来源的基质细胞的迁移活性,从而完成了本发明。

即,本发明涉及:

(1) 肽、其衍生物、它们的药学上可接受的盐或者它们的溶剂合物,所述肽选自:

具有SEQ ID NO: 1~399和403所记载的任意一条氨基酸序列的肽;

在具有SEQ ID NO: 1~399和403所记载的任意一条氨基酸序列的肽中,由添加1个或多个(例如2~40个、2~30个、2~20个、2~10个、2~5个、或者4个、3个或者2个)氨基酸而得到的氨基酸序列构成、并且具有刺激细胞迁移的活性的肽;以及

包含在具有SEQ ID NO: 1~399所记载的任意一条氨基酸序列的肽的第1~42位的氨基酸或者具有SEQ ID NO: 403所记载的氨基酸序列的肽的第1~41位的氨基酸中取代、缺失或***1个或多个(例如2~40个、2~30个、2~20个、2~10个、2~5个、或者4个、3个或者2个)氨基酸而得到的氨基酸序列或者由其构成、并且具有刺激细胞迁移的活性的肽。

(2) 肽、其衍生物、它们的药学上可接受的盐或者它们的溶剂合物,所述肽选自:

具有SEQ ID NO: 1~5、126、128、129、138、167、248、254、280、282、283、292和403所记载的任意一条氨基酸序列的肽;

在具有SEQ ID NO: 1~5、126、128、129、138、167、248、254、280、282、283、292和403所记载的任意一条氨基酸序列的肽中,由添加1个或多个(例如2~40个、2~30个、2~20个、2~10个、2~5个、或者4个、3个或者2个)氨基酸而得到的氨基酸序列构成、并且具有刺激细胞迁移的活性的肽;以及

包含在具有SEQ ID NO: 1~5、126、128、129、138、167、248、254、280、282、283和292所记载的任意一条氨基酸序列的肽的第1~42位氨基酸或者具有SEQ ID NO: 403所记载的氨基酸序列的肽的第1~41位氨基酸中取代、缺失或***1个或多个(例如2~40个、2~30个、2~20个、2~10个、2~5个、或者4个、3个或者2个)氨基酸而得到的氨基酸序列或者由其构成、并且具有刺激细胞迁移的活性的肽。

(3) 肽、其衍生物、它们的药学上可接受的盐或者它们的溶剂合物,所述肽选自:

具有SEQ ID NO: 1~5、167和403所记载的任意一条氨基酸序列的肽;

在具有SEQ ID NO: 1~5、167和403所记载的任意一条氨基酸序列的肽中,由添加1个或多个(例如2~40个、2~30个、2~20个、2~10个、2~5个、或者4个、3个或者2个)氨基酸而得到的氨基酸序列构成、并且具有刺激细胞迁移的活性的肽;以及

包含在具有SEQ ID NO: 1~5和167所记载的任意一条氨基酸序列的肽的第1~42位氨基酸或者具有SEQ ID NO: 403所记载的氨基酸序列的肽的第1~41位氨基酸中取代、缺失或***1个或多个(例如2~40个、2~30个、2~20个、2~10个、2~5个、或者4个、3个或者2个)氨基酸而得到的氨基酸序列或者由其构成、并且具有刺激细胞迁移的活性的肽。

(4) 肽、其衍生物、它们的药学上可接受的盐或者它们的溶剂合物,所述肽选自:

具有SEQ ID NO: 1~5和403所记载的任意一条氨基酸序列的肽;

在具有SEQ ID NO: 1~5和403所记载的任意一条氨基酸序列的肽中,由添加1个或多个(例如2~40个、2~30个、2~20个、2~10个、2~5个、或者4个、3个或者2个)氨基酸而得到的氨基酸序列构成、并且具有刺激细胞迁移的活性的肽;以及

包含在具有SEQ ID NO: 1~5所记载的任意一条氨基酸序列的肽的第1~42位氨基酸或者具有SEQ ID NO: 403所记载的氨基酸序列的肽的第1~41位氨基酸中取代、缺失或***1个或多个(例如2~40个、2~30个、2~20个、2~10个、2~5个、或者4个、3个或者2个)氨基酸而得到的氨基酸序列或者由其构成、并且具有刺激细胞迁移的活性的肽。

(5) 用于刺激PDGFRα阳性细胞迁移的组合物,该组合物含有:上述(1)~(4)中任一项所述的肽、其衍生物、它们的药学上可接受的盐或者它们的溶剂合物。

(6) 用于将骨髓间充质干细胞从骨髄募集到外周血中的组合物,该组合物含有:上述(1)~(4)中任一项所述的肽、其衍生物、它们的药学上可接受的盐或者它们的溶剂合物。

(7) 用于使组织再生的组合物,该组合物含有:上述(1)~(4)中任一项所述的肽、其衍生物、它们的药学上可接受的盐或者它们的溶剂合物。

(8) 用于刺激骨髄来源的基质细胞迁移的组合物,该组合物含有:上述(1)~(4)中任一项所述的肽、其衍生物、它们的药学上可接受的盐或者它们的溶剂合物。

发明效果

本发明的肽例如可用作下述组合物的有效成分:用于刺激PDGFRα阳性细胞迁移的组合物、用于将骨髓间充质干细胞从骨髄募集到外周血中的组合物、用于使组织再生的组合物、或者用于刺激骨髄来源的基质细胞迁移的组合物。

附图说明

[图1] 图1显示6种(人HMGB1的第2位~第44位的肽(2-44)和修饰第43位、第44位的氨基酸而得到的5种肽(肽-1~肽-5))肽的血浆中稳定性试验的结果。P1~P5是指肽-1~肽-5的肽。纵轴显示以刚刚添加血浆后的肽作为100而算出的残留率,横轴显示添加血浆后的时间。需要说明的是,由于2-44的肽在添加血浆后15分钟以后的样品为定量下限(0.5μg/mL)以下,所以在图1中无法将残留率作图。

[图2] 图2是2种肽(人HMGB1的第2位~第44位的肽(2-44)和修饰第43位、第44位的氨基酸而得到的肽(肽-6))的细胞迁移活性的测定结果。NC显示阴性对照。

[图3] 图3显示3种肽(人HMGB1的第2位~第44位的肽(2-44)和修饰第43位、第44位的氨基酸而得到的2种肽(肽-3和6))的血浆中稳定性试验的结果。纵轴显示以刚刚添加血浆后的肽作为100而算出的残留率,横轴显示添加血浆后的时间。

具体实施方式

本发明提供以下(a)~(c)中任一项所述的肽。

(a) 具有SEQ ID NO: 1~399和403所记载的任意一条氨基酸序列的肽;

(b) 在具有SEQ ID NO: 1~399和403所记载的任意一条氨基酸序列的肽中,由添加1个或多个(例如2~40个、2~30个、2~20个、2~10个、2~5个、或者4个、3个或2个)氨基酸而得到的氨基酸序列构成、并且具有刺激细胞迁移的活性的肽;以及

(c) 包含在具有SEQ ID NO: 1~399所记载的任意一条氨基酸序列的肽的第1~42位的氨基酸或者具有SEQ ID NO: 403所记载的氨基酸序列的肽的第1~41位的氨基酸中取代、缺失或***1个或多个(例如2~40个、2~30个、2~20个、2~10个、2~5个、或者4个、3个或2个)氨基酸而得到的氨基酸序列或者由其构成、并且具有刺激细胞迁移的活性的肽。

本发明提供用于刺激PDGFRα阳性细胞或者骨髄来源的基质细胞迁移的组合物,该组合物含有以下(a)~(c)中任一项所述的肽。

(a) 具有SEQ ID NO: 1~399和403所记载的任意一条氨基酸序列的肽;

(b) 在具有SEQ ID NO: 1~399和403所记载的任意一条氨基酸序列的肽中,由添加1个或多个(例如2~40个、2~30个、2~20个、2~10个、2~5个、或者4个、3个或2个)氨基酸而得到的氨基酸序列构成、并且具有刺激细胞迁移的活性的肽;以及

(c) 包含在具有SEQ ID NO: 1~399所记载的任意一条氨基酸序列的肽的第1~42位的氨基酸或者具有SEQ ID NO: 403所记载的氨基酸序列的肽的第1~41位的氨基酸中取代、缺失或***1个或多个(例如2~40个、2~30个、2~20个、2~10个、2~5个、或者4个、3个或2个)氨基酸而得到的氨基酸序列或者由其构成、并且具有刺激细胞迁移的活性的肽。

本发明的用于刺激PDGFRα阳性细胞或者骨髄来源的基质细胞迁移的组合物包括试剂组合物和药物组合物。在本说明书中,试剂组合物还表达为试剂,而药物组合物还表达为药物、药剂或者药学组合物。

本发明的用于刺激PDGFRα阳性细胞或者骨髄来源的基质细胞迁移的试剂组合物例如可用作用于开发再生医疗、再生诱导医疗的基础研究和临床研究所需的试剂。例如,通过使用该试剂组合物,可在实验动物的生物体组织中募集细胞,研究组织修复、组织功能重建的程度。另外,例如通过使用该试剂组合物,可在试管内进行基于细胞募集的组织再生诱导研究。

另外,本发明的用于刺激PDGFRα阳性细胞或者骨髄来源的基质细胞迁移的药物组合物例如可用作再生医疗、再生诱导医疗中的药物。例如,通过使用该药物组合物,可使组织再生。另外,该药物组合物例如可作为所谓的预防药物预防因组织干细胞的减少而引起的组织/脏器功能的下降,或者可作为抗加龄药物(抗衰老药物)延迟加龄性变化的进展。

需要说明的是,在本说明书中,用于刺激PDGFRα阳性细胞或者骨髄来源的基质细胞迁移的组合物还表达为:用于刺激PDGFRα阳性细胞或者骨髄来源的基质细胞迁移的药剂、细胞迁移刺激剂、用于诱导细胞迁移的组合物、用于诱导细胞迁移的药剂、细胞迁移诱导剂、或者细胞诱导剂。

在本发明中,细胞迁移刺激活性是指刺激细胞迁移的活性。在本说明书中,细胞迁移刺激活性还表达为细胞迁移诱导活性或细胞诱导活性。

本发明提供用于将骨髓间充质干细胞从骨髄募集到外周血中的组合物,该组合物含有以下(a)~(c)中任一项所述的物质。

(a) 具有SEQ ID NO: 1~399和403所记载的任意一条氨基酸序列的肽;

(b) 在具有SEQ ID NO: 1~399和403所记载的任意一条氨基酸序列的肽中,由添加1个或多个(例如2~40个、2~30个、2~20个、2~10个、2~5个、或者4个、3个或2个)氨基酸而得到的氨基酸序列构成、并且具有刺激细胞迁移的活性的肽;以及

(c) 包含在具有SEQ ID NO: 1~399所记载的任意一条氨基酸序列的肽的第1~42位的氨基酸或者具有SEQ ID NO: 403所记载的氨基酸序列的肽的第1~41位的氨基酸中取代、缺失或***1个或多个(例如2~40个、2~30个、2~20个、2~10个、2~5个、或者4个、3个或2个)氨基酸而得到的氨基酸序列或者由其构成、并且具有刺激细胞迁移的活性的肽。

本发明的用于将骨髓间充质干细胞从骨髄募集到外周血中的组合物包括试剂组合物和药物组合物。

本发明的用于使组织再生的试剂组合物例如可用作用于开发再生医疗、再生诱导医疗的基础研究和临床研究所需的试剂。另外,本发明的用于使组织再生的药物组合物例如可用作再生医疗、再生诱导医疗中的药物。例如,通过使用该药物组合物,可将骨髄细胞募集到外周循环中使组织再生。另外,例如还可将利用该药物组合物募集到外周血中的细胞回收到体外后进行浓缩,给予到组织进行治疗。在现有方法中,由于是从位于体内深部的骨髄回收细胞,所以对生物体具有侵袭性,但如果使用本发明的药物组合物,则以低侵袭性由外周血回收骨髄细胞,可用于骨髄细胞移植等。需要说明的是,在本说明书中,用于将骨髓间充质干细胞从骨髄募集到外周血中的组合物还表达为:用于将骨髓间充质干细胞从骨髄诱导到外周血中的组合物。

本发明提供用于使组织再生的组合物,该组合物含有以下(a)~(c)中任一项所述的物质。

(a) 具有SEQ ID NO: 1~399和403所记载的任意一条氨基酸序列的肽;

(b) 在具有SEQ ID NO: 1~399和403所记载的任意一条氨基酸序列的肽中,由添加1个或多个(例如2~40个、2~30个、2~20个、2~10个、2~5个、或者4个、3个或2个)氨基酸而得到的氨基酸序列构成、并且具有刺激细胞迁移的活性的肽;以及

(c) 包含在具有SEQ ID NO: 1~399所记载的任意一条氨基酸序列的肽的第1~42位的氨基酸或者具有SEQ ID NO: 403所记载的氨基酸序列的肽的第1~41位的氨基酸中取代、缺失或***1个或多个(例如2~40个、2~30个、2~20个、2~10个、2~5个、或者4个、3个或2个)氨基酸而得到的氨基酸序列或者由其构成、并且具有刺激细胞迁移的活性的肽。

本发明的用于使组织再生的组合物包括试剂组合物和药物组合物。

本发明的用于使组织再生的试剂组合物例如可用作用于开发再生医疗、再生诱导医疗的基础研究和临床研究所需的试剂。另外,本发明的用于使组织再生的药物组合物例如可用作再生医疗、再生诱导医疗中的药物。

需要说明的是,在本说明书中,用于使组织再生的组合物还表达为用于诱导或促进组织再生的组合物、用于诱导或促进组织再生的药剂、组织再生诱导剂或组织再生促进剂。另外,组织再生还包括组织修复。

本发明的用于使组织再生的组合物不挑选给予/添加部位。即,该组合物即使是对需要再生的组织、与需要再生的组织不同的组织、血中等任一组织进行给予,也可发挥其效果。例如,通过给予/添加该组合物,在给予/添加部位或其附近的组织募集细胞,诱导或促进组织再生。另外,例如通过对损伤组织部位或其附近给予/添加该组合物,在该损伤组织募集细胞,诱导或促进组织再生。另外,例如通过对与需要再生的组织不同的组织给予/添加该组合物,骨髄细胞通过外周循环从骨髄募集到需要再生的组织,诱导或促进组织再生。这里,“外周循环”也称作“血液循环”、“外周循环血流”。

作为需要再生的组织,可示例损伤的组织、坏死的组织、术后组织、功能下降的组织、纤维化的组织、老化的组织、患病的组织等,例如可示例生物体皮肤组织、体内活检(手术)组织(脑、肺、心脏、肝脏、胃、小肠、大肠、胰腺、肾脏、膀胱、脾脏、子宫、睾丸或血液等)。

对与需要再生的组织不同的组织给予是指对需要再生的部位以外的部位(与需要再生的部位不同的部位)给予。因此,“与需要再生的组织不同的组织”可表达为:与需要再生的组织不同的部位、与需要再生的部位不同的部位、脱离需要再生的组织的部位、脱离需要再生的部位的部位、远离需要再生的部位的部位、远离需要再生的组织的组织、远端部、远端组织。即,本发明的组合物可有效地用于使难以从体外直接进行给予的组织(脑、心脏等)再生。

在需要再生的组织中募集的细胞分化成各种细胞,有助于需要再生的组织的功能再生和功能维持、功能强化。在本发明中,作为需要再生的组织,可列举:因缺血、贫血/低氧状态引起的各种病态,因外伤、烫伤、炎症、自身免疫、基因异常等而损伤的组织,但并不限于这些原因。

作为本发明中的组织,只要是骨髄来源的细胞可分化的组织即可,没有特别限定,例如可示例:皮肤组织、骨组织、软骨组织、肌肉组织、脂肪组织、心肌组织、神经系统组织、肺组织、消化道组织、肝/胆/胰组织、泌尿/生殖器等生物体内的所有组织。另外,通过使用上述组合物,顽固性皮肤溃疡、皮肤创伤、水疱症、脱毛症等皮肤疾病自不必说,在脑梗塞、心肌梗塞、骨折、肺梗塞、胃溃疡、肠炎等的需要再生的组织中,诱导功能性组织再生的治疗也成为可能。对给予上述组合物的动物种没有特别限定,可列举哺乳类、鸟类、鱼类等。作为哺乳类,可列举人或非人动物,例如可示例:人、小鼠、大鼠、猴、猪、狗、兔、仓鼠、豚鼠、马、绵羊、鲸鱼等,但并不限于这些。

另外,作为与需要再生的组织不同的组织,可示例:血液组织、肌肉组织、皮下组织、皮内组织、腹腔等。

作为神经组织,可列举中枢神经组织,但并不限于此。另外,用于使神经组织再生的组合物例如可用于脑梗塞、脑出血、脑挫伤等的治疗,但并不限于这些。另外,用于使骨组织再生的组合物例如可用于骨折的治疗,但并不限于此。另外,用于使皮肤组织再生的组合物例如可用于皮肤溃疡、手术创伤的缝合不全、烫伤、切伤、挫伤、皮肤糜烂、擦伤等的治疗,但并不限于这些。

另外,在本发明中,作为刺激迁移的细胞或者从骨髄募集到外周血中的细胞,可列举未分化的细胞、处于各种分化阶段的细胞,但并不限于这些。另外,在本发明中,作为刺激迁移的细胞或者从骨髄募集到外周血中的细胞,可列举干细胞、非干细胞等,但并不限于这些。干细胞包括循环性干细胞或非循环性干细胞。作为非循环性干细胞,可示例组织中通常存在的组织干细胞。作为循环性干细胞,可示例血中循环性的干细胞。

另外,作为刺激迁移的细胞或者从骨髄募集到外周血中的细胞,可列举骨髄来源的细胞或者造血干细胞,但并不限于此。在本说明书中,“造血干细胞”是指除了可分化成嗜中性粒细胞、嗜酸性粒细胞、嗜碱性粒细胞、淋巴细胞、单核细胞、巨噬细胞等白细胞以外,还可分化成红细胞、血小板、肥大细胞、树突状细胞等血细胞类细胞的干细胞,作为标志物,人中已知CD34阳性、CD133阳性,小鼠中已知CD34阴性、c-Kit阳性、Sca-1阳性、Lineagemarker阴性。另外,造血干细胞的特征在于:在使用培养皿进行培养的情况下难以单独培养,需要与基质细胞共同培养。

在本说明书中,“骨髄细胞”是指骨髄内存在的细胞,另一方面,“骨髄来源的细胞”是指从骨髄募集或者取出到骨髄外的“骨髄细胞”。“骨髄细胞”包括骨髄中存在的含有组织前体细胞集团的细胞。另外,“骨髄来源的细胞”可以是包括Mesoangioblast(中胚层成血管细胞)在内的细胞,也可以是除Mesoangioblast以外的细胞。

组织前体细胞定义为具有单向分化成血液系统以外的特定组织细胞的能力的未分化细胞,包括具有分化成上述的间充质组织、上皮组织、神经组织、实体脏器、血管内皮的能力的未分化细胞。

“骨髄细胞”、“骨髄来源的细胞”是指造血干细胞和来源于其的白细胞、红细胞、血小板、成骨细胞、纤维细胞(ファイブロサイト)等分化细胞、或者迄今为止称为骨髓间充质干细胞、骨髄间充质基质细胞、骨髄多能基质细胞或骨髄多能干细胞的细胞所代表的干细胞。在本说明书中,“骨髄干细胞”是指骨髄内存在的干细胞,另一方面,“骨髄来源的干细胞”是指从骨髄募集或者取出到骨髄外的“骨髄干细胞”。在本发明中,作为刺激迁移的细胞或者从骨髄募集到外周血中的细胞,可列举“骨髄来源的干细胞”,但并不限于此。“骨髄细胞”、“骨髄来源的细胞”可通过采集骨髄(采集骨髄细胞)、或者采集外周血而进行分离。造血干细胞为非附着细胞,但“骨髄细胞”、“骨髄来源的细胞”的一部分通过采集骨髄(采集骨髄细胞)、采集外周血而得到的血液中的单核细胞组分细胞培养而以附着细胞的形式获得。

另外,“骨髄细胞”、“骨髄来源的细胞”包括间充质干细胞,优选具有分化成成骨细胞(通过诱导分化时识别钙的沉淀可特定)、软骨细胞(通过阿尔新蓝染色阳性、番红-O染色阳性等可特定)、脂肪细胞(通过苏丹III染色阳性可特定)、以及分化成成纤维细胞、平滑肌细胞、基质细胞、腱细胞等间充质细胞、以及分化成神经细胞、上皮细胞(例如表皮角化细胞、肠道上皮细胞表达细胞角蛋白家族)、血管内皮细胞的能力。分化后的细胞并不限于上述细胞,还包括分化成肝脏、肾脏、胰腺等实体脏器细胞的能力。

在本说明书中,“骨髄基质细胞”是指骨髄内存在的细胞中除造血干细胞和来源于其的血细胞类细胞以外的细胞,是指可由骨髄采集、并在培养皿中作为附着细胞进行培养/增殖的细胞。骨髄基质细胞或取出到骨髄外的骨髄来源的基质细胞中包括具有多能性的细胞(骨髄多能基质细胞或骨髄来源的多能基质细胞)。另外,骨髄来源的基质细胞可以是以细胞株的形式建立的细胞。作为形成了细胞株的骨髄来源的基质细胞的例子,可列举ST2细胞(Ogawa等人, EMBO J 1988; 7: 1337-43)等。ST2细胞是具有分化成成骨细胞和脂肪细胞的能力的骨髄来源的多能基质细胞株。

在本说明书中,“骨髓间充质干细胞”这一术语与“骨髄间充质基质细胞”、“骨髄多能基质细胞”和“骨髄多能干细胞”互换使用。在本说明书中,“骨髓间充质干细胞”是指骨髄内存在的细胞,该细胞具有以下特征:由骨髄直接采集或者由其他组织(血液或皮肤、脂肪、其他组织)间接采集,并可在培养皿(塑料或者玻璃制)中作为附着细胞进行培养/增殖,具有分化成骨、软骨、脂肪等间充质组织(间充质干细胞)或骨骼肌、心肌、进一步分化成神经组织、上皮组织(多能干细胞)的能力,是可通过采集骨髄细胞而获取的细胞。

另一方面,从骨髄募集到骨髄外的“骨髄来源的间充质干细胞”、“骨髄来源的间充质基质细胞”、“骨髄来源的多能基质细胞”或者“骨髄来源的多能干细胞”是可通过采集外周血、进一步由脂肪等间充质组织、皮肤等上皮组织、脑等神经组织采集而获取的细胞。

另外,这些细胞还具有以下特征:采集后直接给予、或者对生物体的损伤部给予暂且附着于培养皿的细胞,从而还具有例如分化成构成皮肤的角质形成细胞等的上皮组织、构成脑的神经组织的能力。

骨髓间充质干细胞、骨髄间充质基质细胞、骨髄多能基质细胞、骨髄多能干细胞、或者从骨髄募集到骨髄外的这些细胞,优选具有除了分化成成骨细胞(通过诱导分化时识别钙的沉淀等可特定)、软骨细胞(通过阿尔新蓝染色阳性、番红-O染色阳性等可特定)、脂肪细胞(通过苏丹III染色阳性等可特定)以外、还分化成例如成纤维细胞、平滑肌细胞、骨骼肌细胞、基质细胞、腱细胞等间充质细胞、神经细胞、色素细胞、表皮细胞、毛囊细胞(表达细胞角蛋白家族、毛发角蛋白家族等)、上皮细胞(例如表皮角化细胞、肠道上皮细胞表达细胞角蛋白家族等)、内皮细胞、以及分化成肝脏、肾脏、胰腺等实体脏器细胞的能力,但分化后的细胞并不限于上述细胞。

作为人骨髄细胞、人骨髄来源的细胞,可示例:通过采集骨髄(采集骨髄细胞)、采集外周血、采集脂肪而获取,并可直接或者在分离单核细胞组分后进行培养以附着细胞的形式获取的细胞,但并不限于此。作为人骨髄细胞或者人骨髄来源的细胞(例如骨髓间充质干细胞)的标志物,可示例PDGFRα阳性、PDGFRβ阳性、Lin阴性、CD45阴性、CD44阳性、CD90阳性、CD29阳性、Flk-1阴性、CD105阳性、CD73阳性、CD90阳性、CD71阳性、Stro-1阳性、CD106阳性、CD166阳性、CD31阴性、CD271阳性、CD11b阴性的全部或一部分,但并不限于这些。

另外,作为小鼠骨髄细胞、小鼠骨髄来源的细胞,可示例:通过采集骨髄(采集骨髄细胞)、采集外周血、采集脂肪而获取,并可直接或者在分离单核细胞组分后进行培养以附着细胞的形式获取的细胞,但并不限于此。作为小鼠骨髄细胞或者小鼠骨髄来源的细胞(例如骨髓间充质干细胞)的标志物,可以示例CD44阳性、PDGFRα阳性、PDGFRβ阳性、CD45阴性、Lin阴性、Sca-1阳性、c-kit阴性、CD90阳性、CD29阳性、Flk-1阴性、CD271阳性、CD11b阴性的全部或一部分,但并不限于这些。

在本发明中,作为刺激迁移的细胞或者从骨髄募集到外周血中的细胞,可列举PDGFRα阳性细胞,但并不限于此。另外,作为PDGFRα以外的标志物,可示例CD29阳性、CD44阳性、CD90阳性、CD271阳性、CD11b阴性、Flk-1阴性的全部或一部分,但并不限于这些。作为PDGFRα阳性细胞,可示例:PDGFRα阳性的骨髄来源的细胞、PGFRα阳性的骨髄来源的间充质干细胞、PDGFRα阳性的组织中通常存在的组织细胞(例如可示例成纤维细胞等)、作为PDGFRα阳性的骨髄来源的细胞并通过采集骨髄(采集骨髄细胞)、采集外周血得到的血液中的单核细胞组分细胞培养而以附着细胞的形式获得的细胞等,但并不限于这些。

本发明的组合物除了包含上述(a)~(c)中任一项所记载的肽中的至少一种肽以外,还可以包含其他物质。在本发明的组合物中,作为除上述(a)~(c)所记载的肽中的至少一种肽以外的物质,只要不阻碍细胞迁移刺激活性、细胞募集活性或者组织再生促进活性即可,没有特别限定。例如,在本发明的组合物中,除了包含上述(a)~(c)所记载的肽中的至少一种肽以外,还可以包含:强化上述(a)~(c)所记载的肽的功能的相关分子(组)、抑制上述(a)~(c)所记载的肽的期待效果以外的作用的分子(组)、控制细胞的增殖或分化的因子、强化/维持这些因子或细胞的功能的其他因子。

本发明中的人HMGB1蛋白是指作为来源于人的HMGB1蛋白的由SEQ ID NO: 401所记载的氨基酸序列构成的蛋白。另外,由HMGB1蛋白的第1~44位的氨基酸序列构成的肽是指由SEQ ID NO: 402所记载的氨基酸序列构成的肽。

肽的细胞迁移刺激活性除了通过例如实施例记载的方法进行确认以外,还可通过WO2012/147470中公开的方法进行确认,但并不限于此。

肽的血浆中稳定性例如可以通过实施例所记载的方法进行确认,但并不限于此。

作为本发明的肽,可示例由以下的氨基酸序列构成的肽,但并不限于以下这些。

(1) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSKP(SEQ ID NO: 1)

(2) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSPK(SEQ ID NO: 2)

(3) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSPP(SEQ ID NO: 3)

(4) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSKA(SEQ ID NO: 4)

(5) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSKE(SEQ ID NO: 5)

(6) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSAA(SEQ ID NO: 6)

(7) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSAC(SEQ ID NO: 7)

(8) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSAD(SEQ ID NO: 8)

(9) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSAE(SEQ ID NO: 9)

(10) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSAF(SEQ ID NO: 10)

(11) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSAG(SEQ ID NO: 11)

(12) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSAH(SEQ ID NO: 12)

(13) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSAI(SEQ ID NO: 13)

(14) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSAK(SEQ ID NO: 14)

(15) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSAL(SEQ ID NO: 15)

(16) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSAM(SEQ ID NO: 16)

(17) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSAN(SEQ ID NO: 17)

(18) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSAP(SEQ ID NO: 18)

(19) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSAQ(SEQ ID NO: 19)

(20) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSAR(SEQ ID NO: 20)

(21) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSAS(SEQ ID NO: 21)

(22) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSAT(SEQ ID NO: 22)

(23) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSAV(SEQ ID NO: 23)

(24) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSAW(SEQ ID NO: 24)

(25) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSAY(SEQ ID NO: 25)

(26) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSCA(SEQ ID NO: 26)

(27) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSCC(SEQ ID NO: 27)

(28) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSCD(SEQ ID NO: 28)

(29) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSCE(SEQ ID NO: 29)

(30) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSCF(SEQ ID NO: 30)

(31) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSCG(SEQ ID NO: 31)

(32) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSCH(SEQ ID NO: 32)

(33) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSCI(SEQ ID NO: 33)

(34) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSCK(SEQ ID NO: 34)

(35) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSCL(SEQ ID NO: 35)

(36) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSCM(SEQ ID NO: 36)

(37) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSCN(SEQ ID NO: 37)

(38) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSCP(SEQ ID NO: 38)

(39) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSCQ(SEQ ID NO: 39)

(40) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSCR(SEQ ID NO: 40)

(41) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSCS(SEQ ID NO: 41)

(42) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSCT(SEQ ID NO: 42)

(43) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSCV(SEQ ID NO: 43)

(44) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSCW(SEQ ID NO: 44)

(45) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSCY(SEQ ID NO: 45)

(46) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSDA(SEQ ID NO: 46)

(47) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSDC(SEQ ID NO: 47)

(48) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSDD(SEQ ID NO: 48)

(49) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSDE(SEQ ID NO: 49)

(50) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSDF(SEQ ID NO: 50)

(51) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSDG(SEQ ID NO: 51)

(52) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSDH(SEQ ID NO: 52)

(53) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSDI(SEQ ID NO: 53)

(54) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSDK(SEQ ID NO: 54)

(55) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSDL(SEQ ID NO: 55)

(56) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSDM(SEQ ID NO: 56)

(57) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSDN(SEQ ID NO: 57)

(58) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSDP(SEQ ID NO: 58)

(59) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSDQ(SEQ ID NO: 59)

(60) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSDR(SEQ ID NO: 60)

(61) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSDS(SEQ ID NO: 61)

(62) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSDT(SEQ ID NO: 62)

(63) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSDV(SEQ ID NO: 63)

(64) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSDW(SEQ ID NO: 64)

(65) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSDY(SEQ ID NO: 65)

(66) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSEA(SEQ ID NO: 66)

(67) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSEC(SEQ ID NO: 67)

(68) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSED(SEQ ID NO: 68)

(69) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSEE(SEQ ID NO: 69)

(70) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSEF(SEQ ID NO: 70)

(71) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSEG(SEQ ID NO: 71)

(72) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSEH(SEQ ID NO: 72)

(73) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSEI(SEQ ID NO: 73)

(74) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSEK(SEQ ID NO: 74)

(75) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSEL(SEQ ID NO: 75)

(76) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSEM(SEQ ID NO: 76)

(77) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSEN(SEQ ID NO: 77)

(78) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSEP(SEQ ID NO: 78)

(79) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSEQ(SEQ ID NO: 79)

(80) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSER(SEQ ID NO: 80)

(81) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSES(SEQ ID NO: 81)

(82) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSET(SEQ ID NO: 82)

(83) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSEV(SEQ ID NO: 83)

(84) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSEW(SEQ ID NO: 84)

(85) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSEY(SEQ ID NO: 85)

(86) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSFA(SEQ ID NO: 86)

(87) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSFC(SEQ ID NO: 87)

(88) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSFD(SEQ ID NO: 88)

(89) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSFE(SEQ ID NO: 89)

(90) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSFF(SEQ ID NO: 90)

(91) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSFG(SEQ ID NO: 91)

(92) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSFH(SEQ ID NO: 92)

(93) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSFI(SEQ ID NO: 93)

(94) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSFK(SEQ ID NO: 94)

(95) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSFL(SEQ ID NO: 95)

(96) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSFM(SEQ ID NO: 96)

(97) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSFN(SEQ ID NO: 97)

(98) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSFP(SEQ ID NO: 98)

(99) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSFQ(SEQ ID NO: 99)

(100) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSFR(SEQ ID NO: 100)

(101) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSFS(SEQ ID NO: 101)

(102) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSFT(SEQ ID NO: 102)

(103) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSFV(SEQ ID NO: 103)

(104) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSFW(SEQ ID NO: 104)

(105) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSFY(SEQ ID NO: 105)

(106) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSGA(SEQ ID NO: 106)

(107) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSGC(SEQ ID NO: 107)

(108) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSGD(SEQ ID NO: 108)

(109) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSGE(SEQ ID NO: 109)

(110) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSGF(SEQ ID NO: 110)

(111) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSGG(SEQ ID NO: 111)

(112) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSGH(SEQ ID NO: 112)

(113) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSGI(SEQ ID NO: 113)

(114) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSGK(SEQ ID NO: 114)

(115) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSGL(SEQ ID NO: 115)

(116) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSGM(SEQ ID NO: 116)

(117) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSGN(SEQ ID NO: 117)

(118) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSGP(SEQ ID NO: 118)

(119) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSGQ(SEQ ID NO: 119)

(120) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSGR(SEQ ID NO: 120)

(121) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSGS(SEQ ID NO: 121)

(122) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSGT(SEQ ID NO: 122)

(123) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSGV(SEQ ID NO: 123)

(124) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSGW(SEQ ID NO: 124)

(125) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSGY(SEQ ID NO: 125)

(126) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSHA(SEQ ID NO: 126)

(127) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSHC(SEQ ID NO: 127)

(128) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSHD(SEQ ID NO: 128)

(129) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSHE(SEQ ID NO: 129)

(130) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSHF(SEQ ID NO: 130)

(131) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSHG(SEQ ID NO: 131)

(132) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSHH(SEQ ID NO: 132)

(133) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSHI(SEQ ID NO: 133)

(134) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSHK(SEQ ID NO: 134)

(135) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSHL(SEQ ID NO: 135)

(136) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSHM(SEQ ID NO: 136)

(137) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSHN(SEQ ID NO: 137)

(138) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSHP(SEQ ID NO: 138)

(139) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSHQ(SEQ ID NO: 139)

(140) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSHR(SEQ ID NO: 140)

(141) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSHS(SEQ ID NO: 141)

(142) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSHT(SEQ ID NO: 142)

(143) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSHV(SEQ ID NO: 143)

(144) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSHW(SEQ ID NO: 144)

(145) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSHY(SEQ ID NO: 145)

(146) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSIA(SEQ ID NO: 146)

(147) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSIC(SEQ ID NO: 147)

(148) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSID(SEQ ID NO: 148)

(149) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSIE(SEQ ID NO: 149)

(150) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSIF(SEQ ID NO: 150)

(151) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSIG(SEQ ID NO: 151)

(152) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSIH(SEQ ID NO: 152)

(153) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSII(SEQ ID NO: 153)

(154) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSIK(SEQ ID NO: 154)

(155) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSIL(SEQ ID NO: 155)

(156) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSIM(SEQ ID NO: 156)

(157) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSIN(SEQ ID NO: 157)

(158) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSIP(SEQ ID NO: 158)

(159) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSIQ(SEQ ID NO: 159)

(160) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSIR(SEQ ID NO: 160)

(161) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSIS(SEQ ID NO: 161)

(162) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSIT(SEQ ID NO: 162)

(163) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSIV(SEQ ID NO: 163)

(164) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSIW(SEQ ID NO: 164)

(165) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSIY(SEQ ID NO: 165)

(166) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSKC(SEQ ID NO: 166)

(167) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSKD(SEQ ID NO: 167)

(168) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSKF(SEQ ID NO: 168)

(169) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSKG(SEQ ID NO: 169)

(170) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSKH(SEQ ID NO: 170)

(171) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSKI(SEQ ID NO: 171)

(172) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSKL(SEQ ID NO: 172)

(173) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSKM(SEQ ID NO: 173)

(174) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSKN(SEQ ID NO: 174)

(175) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSKQ(SEQ ID NO: 175)

(176) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSKR(SEQ ID NO: 176)

(177) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSKS(SEQ ID NO: 177)

(178) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSKT(SEQ ID NO: 178)

(179) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSKV(SEQ ID NO: 179)

(180) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSKW(SEQ ID NO: 180)

(181) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSKY(SEQ ID NO: 181)

(182) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSLA(SEQ ID NO: 182)

(183) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSLC(SEQ ID NO: 183)

(184) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSLD(SEQ ID NO: 184)

(185) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSLE(SEQ ID NO: 185)

(186) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSLF(SEQ ID NO: 186)

(187) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSLG(SEQ ID NO: 187)

(188) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSLH(SEQ ID NO: 188)

(189) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSLI(SEQ ID NO: 189)

(190) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSLK(SEQ ID NO: 190)

(191) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSLL(SEQ ID NO: 191)

(192) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSLM(SEQ ID NO: 192)

(193) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSLN(SEQ ID NO: 193)

(194) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSLP(SEQ ID NO: 194)

(195) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSLQ(SEQ ID NO: 195)

(196) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSLR(SEQ ID NO: 196)

(197) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSLS(SEQ ID NO: 197)

(198) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSLT(SEQ ID NO: 198)

(199) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSLV(SEQ ID NO: 199)

(200) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSLW(SEQ ID NO: 200)

(201) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSLY(SEQ ID NO: 201)

(202) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSMA(SEQ ID NO: 202)

(203) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSMC(SEQ ID NO: 203)

(204) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSMD(SEQ ID NO: 204)

(205) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSME(SEQ ID NO: 205)

(206) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSMF(SEQ ID NO: 206)

(207) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSMG(SEQ ID NO: 207)

(208) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSMH(SEQ ID NO: 208)

(209) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSMI(SEQ ID NO: 209)

(210) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSMK(SEQ ID NO: 210)

(211) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSML(SEQ ID NO: 211)

(212) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSMM(SEQ ID NO: 212)

(213) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSMN(SEQ ID NO: 213)

(214) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSMP(SEQ ID NO: 214)

(215) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSMQ(SEQ ID NO: 215)

(216) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSMR(SEQ ID NO: 216)

(217) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSMS(SEQ ID NO: 217)

(218) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSMT(SEQ ID NO: 218)

(219) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSMV(SEQ ID NO: 219)

(220) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSMW(SEQ ID NO: 220)

(221) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSMY(SEQ ID NO: 221)

(222) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSNA(SEQ ID NO: 222)

(223) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSNC(SEQ ID NO: 223)

(224) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSND(SEQ ID NO: 224)

(225) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSNE(SEQ ID NO: 225)

(226) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSNF(SEQ ID NO: 226)

(227) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSNG(SEQ ID NO: 227)

(228) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSNH(SEQ ID NO: 228)

(229) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSNI(SEQ ID NO: 229)

(230) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSNK(SEQ ID NO: 230)

(231) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSNL(SEQ ID NO: 231)

(232) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSNM(SEQ ID NO: 232)

(233) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSNN(SEQ ID NO: 233)

(234) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSNP(SEQ ID NO: 234)

(235) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSNQ(SEQ ID NO: 235)

(236) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSNR(SEQ ID NO: 236)

(237) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSNS(SEQ ID NO: 237)

(238) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSNT(SEQ ID NO: 238)

(239) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSNV(SEQ ID NO: 239)

(240) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSNW(SEQ ID NO: 240)

(241) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSNY(SEQ ID NO: 241)

(242) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSPA(SEQ ID NO: 242)

(243) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSPC(SEQ ID NO: 243)

(244) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSPD(SEQ ID NO: 244)

(245) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSPE(SEQ ID NO: 245)

(246) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSPF(SEQ ID NO: 246)

(247) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSPG(SEQ ID NO: 247)

(248) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSPH(SEQ ID NO: 248)

(249) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSPI(SEQ ID NO: 249)

(250) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSPL(SEQ ID NO: 250)

(251) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSPM(SEQ ID NO: 251)

(252) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSPN(SEQ ID NO: 252)

(253) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSPQ(SEQ ID NO: 253)

(254) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSPR(SEQ ID NO: 254)

(255) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSPS(SEQ ID NO: 255)

(256) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSPT(SEQ ID NO: 256)

(257) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSPV(SEQ ID NO: 257)

(258) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSPW(SEQ ID NO: 258)

(259) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSPY(SEQ ID NO: 259)

(260) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSQA(SEQ ID NO: 260)

(261) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSQC(SEQ ID NO: 261)

(262) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSQD(SEQ ID NO: 262)

(263) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSQE(SEQ ID NO: 263)

(264) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSQF(SEQ ID NO: 264)

(265) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSQG(SEQ ID NO: 265)

(266) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSQH(SEQ ID NO: 266)

(267) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSQI(SEQ ID NO: 267)

(268) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSQK(SEQ ID NO: 268)

(269) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSQL(SEQ ID NO: 269)

(270) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSQM(SEQ ID NO: 270)

(271) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSQN(SEQ ID NO: 271)

(272) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSQP(SEQ ID NO: 272)

(273) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSQQ(SEQ ID NO: 273)

(274) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSQR(SEQ ID NO: 274)

(275) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSQS(SEQ ID NO: 275)

(276) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSQT(SEQ ID NO: 276)

(277) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSQV(SEQ ID NO: 277)

(278) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSQW(SEQ ID NO: 278)

(279) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSQY(SEQ ID NO: 279)

(280) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSRA(SEQ ID NO: 280)

(281) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSRC(SEQ ID NO: 281)

(282) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSRD(SEQ ID NO: 282)

(283) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSRE(SEQ ID NO: 283)

(284) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSRF(SEQ ID NO: 284)

(285) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSRG(SEQ ID NO: 285)

(286) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSRH(SEQ ID NO: 286)

(287) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSRI(SEQ ID NO: 287)

(288) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSRK(SEQ ID NO: 288)

(289) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSRL(SEQ ID NO: 289)

(290) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSRM(SEQ ID NO: 290)

(291) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSRN(SEQ ID NO: 291)

(292) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSRP(SEQ ID NO: 292)

(293) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSRQ(SEQ ID NO: 293)

(294) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSRR(SEQ ID NO: 294)

(295) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSRS(SEQ ID NO: 295)

(296) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSRT(SEQ ID NO: 296)

(297) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSRV(SEQ ID NO: 297)

(298) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSRW(SEQ ID NO: 298)

(299) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSRY(SEQ ID NO: 299)

(300) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSSA(SEQ ID NO: 300)

(301) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSSC(SEQ ID NO: 301)

(302) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSSD(SEQ ID NO: 302)

(303) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSSE(SEQ ID NO: 303)

(304) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSSF(SEQ ID NO: 304)

(305) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSSG(SEQ ID NO: 305)

(306) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSSH(SEQ ID NO: 306)

(307) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSSI(SEQ ID NO: 307)

(308) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSSK(SEQ ID NO: 308)

(309) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSSL(SEQ ID NO: 309)

(310) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSSM(SEQ ID NO: 310)

(311) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSSN(SEQ ID NO: 311)

(312) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSSP(SEQ ID NO: 312)

(313) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSSQ(SEQ ID NO: 313)

(314) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSSR(SEQ ID NO: 314)

(315) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSSS(SEQ ID NO: 315)

(316) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSST(SEQ ID NO: 316)

(317) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSSV(SEQ ID NO: 317)

(318) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSSW(SEQ ID NO: 318)

(319) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSSY(SEQ ID NO: 319)

(320) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSTA(SEQ ID NO: 320)

(321) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSTC(SEQ ID NO: 321)

(322) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSTD(SEQ ID NO: 322)

(323) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSTE(SEQ ID NO: 323)

(324) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSTF(SEQ ID NO: 324)

(325) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSTG(SEQ ID NO: 325)

(326) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSTH(SEQ ID NO: 326)

(327) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSTI(SEQ ID NO: 327)

(328) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSTK(SEQ ID NO: 328)

(329) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSTL(SEQ ID NO: 329)

(330) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSTM(SEQ ID NO: 330)

(331) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSTN(SEQ ID NO: 331)

(332) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSTP(SEQ ID NO: 332)

(333) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSTQ(SEQ ID NO: 333)

(334) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSTR(SEQ ID NO: 334)

(335) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSTS(SEQ ID NO: 335)

(336) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSTT(SEQ ID NO: 336)

(337) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSTV(SEQ ID NO: 337)

(338) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSTW(SEQ ID NO: 338)

(339) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSTY(SEQ ID NO: 339)

(340) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSVA(SEQ ID NO: 340)

(341) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSVC(SEQ ID NO: 341)

(342) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSVD(SEQ ID NO: 342)

(343) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSVE(SEQ ID NO: 343)

(344) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSVF(SEQ ID NO: 344)

(345) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSVG(SEQ ID NO: 345)

(346) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSVH(SEQ ID NO: 346)

(347) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSVI(SEQ ID NO: 347)

(348) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSVK(SEQ ID NO: 348)

(349) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSVL(SEQ ID NO: 349)

(350) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSVM(SEQ ID NO: 350)

(351) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSVN(SEQ ID NO: 351)

(352) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSVP(SEQ ID NO: 352)

(353) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSVQ(SEQ ID NO: 353)

(354) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSVR(SEQ ID NO: 354)

(355) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSVS(SEQ ID NO: 355)

(356) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSVT(SEQ ID NO: 356)

(357) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSVV(SEQ ID NO: 357)

(358) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSVW(SEQ ID NO: 358)

(359) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSVY(SEQ ID NO: 359)

(360) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSWA(SEQ ID NO: 360)

(361) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSWC(SEQ ID NO: 361)

(362) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSWD(SEQ ID NO: 362)

(363) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSWE(SEQ ID NO: 363)

(364) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSWF(SEQ ID NO: 364)

(365) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSWG(SEQ ID NO: 365)

(366) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSWH(SEQ ID NO: 366)

(367) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSWI(SEQ ID NO: 367)

(368) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSWK(SEQ ID NO: 368)

(369) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSWL(SEQ ID NO: 369)

(370) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSWM(SEQ ID NO: 370)

(371) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSWN(SEQ ID NO: 371)

(372) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSWP(SEQ ID NO: 372)

(373) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSWQ(SEQ ID NO: 373)

(374) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSWR(SEQ ID NO: 374)

(375) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSWS(SEQ ID NO: 375)

(376) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSWT(SEQ ID NO: 376)

(377) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSWV(SEQ ID NO: 377)

(378) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSWW(SEQ ID NO: 378)

(379) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSWY(SEQ ID NO: 379)

(380) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSYA(SEQ ID NO: 380)

(381) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSYC(SEQ ID NO: 381)

(382) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSYD(SEQ ID NO: 382)

(383) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSYE(SEQ ID NO: 383)

(384) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSYF(SEQ ID NO: 384)

(385) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSYG(SEQ ID NO: 385)

(386) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSYH(SEQ ID NO: 386)

(387) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSYI(SEQ ID NO: 387)

(388) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSYK(SEQ ID NO: 388)

(389) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSYL(SEQ ID NO: 389)

(390) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSYM(SEQ ID NO: 390)

(391) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSYN(SEQ ID NO: 391)

(392) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSYP(SEQ ID NO: 392)

(393) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSYQ(SEQ ID NO: 393)

(394) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSYR(SEQ ID NO: 394)

(395) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSYS(SEQ ID NO: 395)

(396) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSYT(SEQ ID NO: 396)

(397) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSYV(SEQ ID NO: 397)

(398) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSYW(SEQ ID NO: 398)

(399) MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSYY(SEQ ID NO: 399)

(400) GKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSPP(SEQ ID NO: 403)

作为本发明的肽,还包括:进一步将上述SEQ ID NO: 1~399所记载的肽的第43位和/或第44位的氨基酸取代成非天然氨基酸而得到的肽、或者将上述SEQ ID NO: 403所记载的肽的第42位和/或第43位的氨基酸取代成非天然氨基酸而得到的肽。

本发明的肽可以是在具有SEQ ID NO: 1~5所记载的任意一条氨基酸序列的肽中具有氨基酸的保守取代的肽。保守取代是指取代成具有与原始氨基酸在化学上类似的结构或特性的其他氨基酸、而实质上未改变肽的功能的取代。作为保守取代的例子,可以列举:作为酸性氨基酸的天冬氨酸与谷氨酸之间的相互取代、作为碱性氨基酸的赖氨酸、精氨酸和组氨酸之间的相互取代、作为亲水性氨基酸的丝氨酸、苏氨酸、天冬酰胺和谷氨酰胺之间的相互取代等。例如,SEQ ID NO: 167的肽是将SEQ ID NO: 5的肽的第44位的谷氨酸(E)取代成天冬氨酸(D)而得到的肽,认为其与SEQ ID NO: 5的肽具有同等的功能。而且,SEQ IDNO: 126、128、129、138、248、254、280、282、283和292所记载的肽也是在具有SEQ ID NO: 1~5所记载的任意一条氨基酸序列的肽中具有氨基酸的保守取代的肽,认为其与SEQ IDNO: 1~5所记载的任一种肽具有同等的功能。在一个方案中,本发明的肽是具有SEQ IDNO: 1~5、126、128、129、138、167、248、254、280、282、283、292和403所记载的任意一条氨基酸序列的肽。从可以期待更可靠地具有上述功能的角度考虑,在更优选的一个方案中,本发明的肽是具有SEQ ID NO: 1~5、167和403所记载的任意一条氨基酸序列的肽,在进一步优选的一个方案中,本发明的肽是具有SEQ ID NO: 1~5和403所记载的任意一条氨基酸序列的肽。

因此,上述(a)中规定的肽的一个优选方案为具有SEQ ID NO: 1~5、126、128、129、138、167、248、254、280、282、283、292和403所记载的任意一条氨基酸序列的肽,更优选的一个方案为具有SEQ ID NO: 1~5、167和403所记载的任意一条氨基酸序列的肽,进一步优选的一个方案为具有SEQ ID NO: 1~5和403所记载的任意一条氨基酸序列的肽。

而且,上述(b)中规定的肽的一个优选方案为:在具有SEQ ID NO: 1~5、126、128、129、138、167、248、254、280、282、283、292和403所记载的任意一条氨基酸序列的肽中,由添加1个或多个(例如2~40个、2~30个、2~20个、2~10个、2~5个、或者4个、3个或2个)氨基酸而得到的氨基酸序列构成、并且具有刺激细胞迁移的活性的肽,更优选的一个方案为:在具有SEQ ID NO: 1~5、167和403所记载的任意一条氨基酸序列的肽中,由添加1个或多个(例如2~40个、2~30个、2~20个、2~10个、2~5个、或者4个、3个或2个)氨基酸而得到的氨基酸序列构成、并且具有刺激细胞迁移的活性的肽,进一步优选的一个方案为:在具有SEQID NO: 1~5和403所记载的任意一条氨基酸序列的肽中,由添加1个或多个(例如2~40个、2~30个、2~20个、2~10个、2~5个、或者4个、3个或2个)氨基酸而得到的氨基酸序列构成、并且具有刺激细胞迁移的活性的肽。

而且,上述(c)中规定的肽的一个优选方案为:包含在具有SEQ ID NO: 1~5、126、128、129、138和167、248、254、280、282、283和292所记载的任意一条氨基酸序列的肽的第1~42位的氨基酸或者具有SEQ ID NO: 403所记载的氨基酸序列的肽的第1~41位的氨基酸中取代、缺失或***1个或多个(例如2~40个、2~30个、2~20个、2~10个、2~5个、或者4个、3个或2个)氨基酸而得到的氨基酸序列或者由其构成、并且具有刺激细胞迁移的活性的肽,更优选的一个方案为:包含在具有SEQ ID NO: 1~5和167所记载的任意一条氨基酸序列的肽的第1~42位的氨基酸或者具有SEQ ID NO: 403所记载的氨基酸序列的肽的第1~41位的氨基酸中取代、缺失或***1个或多个(例如2~40个、2~30个、2~20个、2~10个、2~5个、或者4个、3个或2个)氨基酸而得到的氨基酸序列或者由其构成、并且具有刺激细胞迁移的活性的肽,进一步优选的一个方案为:包含在具有SEQ ID NO: 1~5所记载的任意一条氨基酸序列的肽的第1~42位的氨基酸或者具有SEQ ID NO: 403所记载的氨基酸序列的肽的第1~41位的氨基酸中取代、缺失或***1个或多个(例如2~40个、2~30个、2~20个、2~10个、2~5个、或者4个、3个或2个)氨基酸而得到的氨基酸序列或者由其构成、并且具有刺激细胞迁移的活性的肽。

本发明的肽的“衍生物”是指,实质上与本发明的肽具有相同的生物学功能或活性、即刺激细胞迁移的活性的肽。该肽的衍生物的C末端可以是羧基、羧酸盐(カルボキシレート)、酰胺或酯的任一种。例如可以列举:添加修饰基而得到的修饰肽、通过修饰氨基酸残基而得到的突变体肽等。

作为修饰基,可以列举:呈荧光性的官能团、不参与肽的立体结构形成的官能团等。另外,可以是天然来源的构成本发明的肽的氨基酸残基以外的氨基酸残基(例如β-丙氨酸等)。作为呈荧光性的官能团,可以列举伊红或异硫氰酸荧光素(FITC)等。作为不参与肽的立体结构形成的官能团,可以列举β-丙氨酸残基等所代表的间隔基等。所述官能团优选存在于末端。而且,“衍生物”还包括经聚乙二醇(PEG)修饰的肽。

作为本发明的肽的“药学上可接受的盐”,可以列举与酸或碱形成的生理学上可接受的盐,尤其优选酸加成盐。作为这样的盐,例如可使用:与盐酸、磷酸、氢溴酸、硫酸等无机酸的盐;或者与乙酸、甲酸、丙酸、富马酸、马来酸、琥珀酸、酒石酸、枸橼酸、苹果酸、草酸、苯甲酸、甲磺酸、苯磺酸等有机酸的盐等。

作为本发明的肽或上述盐的“溶剂合物”,可列举在本发明的肽上配位有任意数目的溶剂分子的溶剂合物,优选为水合物。

本发明提供上述的肽。在本发明中的肽的合成中,可以通过肽液相合成法和肽固相合成法中的任一种方法进行肽的化学合成。在本发明中,优选通过肽固相合成法合成的肽。肽固相合成法是在化学合成肽时通常采用的方法之一,例如可如下实施:使用表面经氨基修饰的直径为0.1mm左右的聚苯乙烯高分子凝胶的珠粒等作为固相,从这里开始通过脱水反应一个个地延伸氨基酸链。一旦做好了目标肽的序列,则将其从固相表面切下,得到目标物质。

通过固相合成法还可进行:在细菌中难以合成的核糖体肽的合成、或者D型或重原子取代体等非天然氨基酸的导入、肽和蛋白主链的修饰等。在固相法中合成70个~超过100个的长肽链的情况下,可以采用天然化学连接法,通过使2条肽链结合来进行合成。

本发明的组合物的给予方法可列举口服给予或胃肠外给予,作为胃肠外给予方法,具体而言,可列举注射给予、经鼻给予、经肺给予、经皮给予等,但并不限于这些。作为注射给予的例子,例如可通过静脉内注射、肌肉内注射、腹腔内注射、皮下注射等将本发明的组合物进行全身或局部(例如,皮下、皮内、皮肤表面、眼球或眼睑结膜、鼻腔粘膜、口腔内和消化道粘膜、***/子宫内粘膜、或者损伤部位等)给予。

另外,作为本发明组合物的给予方法,例如可示例血管内给予(动脉内给予、静脉内给予等)、血液内给予、肌肉内给予、皮下给予、皮内给予、腹腔内给予,但并不限于这些。

另外,对给予部位没有限定,可示例:需要再生的组织部位或其附近、与需要再生的组织不同的部位、或者远离需要再生的组织且不同的部位。例如可列举:血中(动脉内、静脉内等)、肌肉、皮下、皮内、腹腔内,但并不限于这些。

另外,可以根据患者的年龄、症状选择适当的给予方法。在给予本发明的肽的情况下,例如每次给予可以在0.0000001mg~1000mg/kg体重的范围选择给予量。或者,例如每名患者可以在0.00001~100000mg/人的范围选择给予量。在给予分泌本发明的肽的细胞或***有编码该肽的DNA的基因治疗用载体的情况下,以该肽的量达到上述范围内的方式进行给予。然而,本发明的药物组合物并不受这些给予量的限定。

本发明的药物组合物可以按照常规方法制成制剂(例如Remington’sPharmaceutical Science, 最新版, Mark Publishing Company, Easton, U.S.A),可以同时含有药学上可接受的载体或添加剂。例如可列举:表面活性剂、赋形剂、着色剂、着香料、保存剂、稳定剂、缓冲剂、悬浮剂、等渗剂、粘合剂、崩解剂、润滑剂、流动性促进剂、矫味剂等,但并不限于这些,可适当使用其他的常用载体。具体而言,可列举:轻质硅酸酐、乳糖、结晶纤维素、甘露醇、淀粉、羧甲基纤维素钙、羧甲基纤维素钠、羟丙基纤维素、羟丙基甲基纤维素、聚乙烯醇缩醛二乙氨基乙酸酯、聚乙烯吡咯烷酮、明胶、中链脂肪酸甘油三酯、聚氧乙烯氢化蓖麻油60、蔗糖、羧甲基纤维素、玉米淀粉、无机盐类等。

需要说明的是,本说明书中引用的全部的现有技术文献均作为参照而纳入本说明书中。

实施例

通过以下的实施例进一步示例本发明,但本发明并不受下述实施例的限定。

实施例1

各种HMGB1肽的合成

通过固相法合成了:由人HMGB1的第2位~第44位的氨基酸构成的肽(2-44)和在人HMGB1的第1位~第44位的肽中取代第43位和/或第44位的氨基酸序列而得到的以下5种肽(肽-1~肽-5)。

2-44 GKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSKK(SEQ ID NO: 400);

肽-1 MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSKP(SEQ ID NO: 1);

肽-2 MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSPK(SEQ ID NO: 2);

肽-3 MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSPP(SEQ ID NO: 3);

肽-4 MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSKA(SEQ ID NO: 4);

肽-5 MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSKE(SEQ ID NO: 5)。

实施例2

细胞迁移活性测定

使用TrypLE Express (Thermo Fisher Scientific)从皿中剥离作为小鼠骨髄来源的基质细胞株的ST2细胞(RCB0224,理化学研究所生物资源中心)后,通过25℃、1500rpm、5分钟的离心进行回收。使用RPMI1640/10%FBS/1%PenStrep(Gibco)将细胞沉淀物(Cellpellet)调制成7×105细胞/mL,以70μL/插件孔接种在放有培养插件(Culture-insert)(日本Genetics)的24孔板上。24小时后抽出培养插件,用RPMI1640清洗1次。添加550μL经测定培养基(RPMI1640/0.1%FBS)调制成10μM的各肽样品(人HMGB1的第2位~第44位的肽(2-44)、实施例1中制作的5种修饰肽即肽-1~肽-5),进一步培养一夜。阴性对照(NC)只添加了测定培养基。培养后,对细胞进行固定/DiffQuik染色并拍照。根据所拍摄的图像,按照5个等级的评分(-、±、+、++、+++)评价各组的细胞迁移度。另外,在同一条件下对各肽样品均进行了3次试验。

结果

在确认人HMGB1的第2位~第44位的肽(2-44)、实施例1中制作的5种修饰肽即肽-1~肽-5和NC是否具有迁移活性时,5种修饰肽的任意一种均观察到迁移活性(表1)。

[表1]

第1次 第2次 第3次
NC - ± -
2-44 +++ +++ +++
肽-1 +++ + +++
肽-2 +++ ++ +++
肽-3 + + +
肽-4 ++ + +++
肽-5 ++ ++ ++

实施例3

肽在血浆中的稳定性

将使用抗凝剂EDTA·2K由Crl:CD(SD)大鼠采集的全血离心,得到了空白血浆。所得的血浆在冰上保管,仅在稳定性试验当天使用。

将实施例2中使用的6种肽分别以1mg/mL溶解在0.1%TFA水溶液中得到原液,使用蒸馏水由该原液调制溶液,使溶液调制成375μg/mL。相对于1184μL空白血浆添加16μL该溶液,调制了稳定性试验用样品(测定浓度:5μg/mL)。将稳定性试验用样品在冰上静置,在刚刚添加后、1、3、5、15、30、60分钟后采集50μL(各时间点、3例)。相对于所采集的50μL样品,加入250μL的270mmol/L枸橼酸溶液/130mmol/L EDTA·2K水溶液(4:1、v/v)、25μL的0.1%TFA水溶液、25μL IS溶液(人HMGB1的第1位~第44位的肽中第18位、第38位、第41位的苯丙氨酸的9个碳原子、1个氮原子分别取代成稳定同位素的化合物的4μg/mL 0.1%TFA水溶液),进行混合。相对于混合物加入350μL甲醇进行混合后,进一步加入100μL乙腈进行混合,用干冰暂且冷冻。在室温下溶化并进行离心,将所得上清转移到另一容器中进行搅拌,以所得物质作为测定用样品。

将测定用样品导入高效液相色谱仪-串联四极型质谱仪中,检测各肽所特有的监测离子。由另外调制的浓度已知的样品在0.1-10μg/mL的浓度范围制作标准曲线,测定各样品,由所得色谱图的峰面积进行逆回归,得到了样品中的肽浓度。将各时间点的肽浓度进行平均,将以刚刚添加后作为100而算出的残留率(%)对添加后时间作图(图1)。

结果

人HMGB1的第2位~第44位的肽(2-44)和修饰了第43位、第44位的氨基酸的5种肽(肽-1~肽-5)在大鼠血浆中(冰上)的稳定性试验的结果,2-44在添加后15分钟以后的样品为定量下限(0.5μg/mL)以下。另一方面可以确认到:与2-44相比,肽-1~肽-5的5种修饰肽的任意一种均稳定(图1)。

实施例4

HMGB1肽的合成

通过固相法合成了由在人HMGB1的第2位~第44位的肽(2-44)中取代C末端的2个氨基酸而得到的下述序列构成的肽(肽-6)。

肽-6 GKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSPP(SEQ ID NO: 403)。

实施例5

细胞迁移活性测定

使用2.5g/L‐胰蛋白酶/1mmol/L‐EDTA溶液(nacalai tesque)从皿中剥离作为小鼠骨髄来源的基质细胞株的ST2细胞(RCB0224,理化学研究所生物资源中心)后,通过25℃、200g、3分钟的离心进行回收。将细胞沉淀物用RPMI1640/10%FBS/1%PenStrep (nacalaitesque)调制成8.6×105细胞/mL,以70μL/插件孔接种在放有培养插件(日本Genetics)的24孔板上。18小时后,抽出培养插件,用RPMI1640清洗1次。添加1000μL经测定培养基(RPMI1640/0.1%FBS)调制成20μM的各肽样品(人HMGB1的第2位~第44位的肽(2-44)和实施例4中制作的修饰肽即肽-6),进一步培养20小时。阴性对照(NC)仅添加了测定培养基。在刚刚添加测定培养基后和培养20小时后拍摄细胞。根据拍摄的图像,以20小时迁移至该区域的细胞所占的面积相对于通过培养插件制作的空白区域(在添加测定培养基的时间点不存在细胞的区域)的面积的比例(%)之形式,评价了各组的细胞迁移度。

结果

在确认人HMGB1的第2位~第44位的肽(2-44)、实施例4中制作的修饰肽(肽-6)和NC是否存在迁移活性时,在修饰肽(肽-6)中观察到与人HMGB1的第2位~第44位的肽(2-44)同等的迁移活性(图2)。

实施例6

肽在血浆中的稳定性

在预先装有60μL 10%EDTA·2K的5mL管中装入由Crl:CD(SD)大鼠采集的3mL全血,在室温下静置30分钟后,在3000rpm(1600×g)、4℃下离心10分钟,回收上清,作为空白血浆。所得血浆在冰上保管,仅在稳定性试验当天使用。

将人HMGB1的第2位~第44位的肽(以下记作2-44)、实施例1中制作的修饰肽(肽-3)和实施例4中制作的修饰肽(肽-6)分别以1mg/mL溶解于0.1%TFA水溶液中得到原液,使用蒸馏水由该原液调制溶液,使溶液调制成375μg/mL。相对于592μL空白血浆添加8μL该溶液,调制了稳定性试验用样品(测定浓度:5μg/mL)。将稳定性试验用样品在冰上静置,在刚刚添加后、30分钟后和60分钟后采集50μL。相对于采集的50μL样品,加入250μL的270mmol/L枸橼酸溶液/130mmol/L EDTA·2K水溶液(4:1、v/v)、50μL的 0.1%TFA水溶液,进行混合。相对于混合物加入350μL甲醇进行混合后,进一步加入100μL乙腈进行混合,在干冰上暂且冷冻。5~60分钟后,将该样品在室温下溶化,在14000×g、4℃下离心3分钟,采集400μL所得的上清,用离心式浓缩机(Spin dryer light VC-36R、TIETECH株式会社制造)进行干固,之后溶解于200μL的1%TFA/2%CAN缓冲液中,进行滤器过滤(0.22μm),以所得滤液作为测定用样品。

将测定用样品导入高效液相色谱仪-单四极型质谱仪中,检测各肽所特有的监测离子。由另外调制的浓度已知的样品在0.1-10μg/mL的浓度范围制作标准曲线,测定各样品,由所得色谱图的峰面积进行逆回归,得到了样品中的肽浓度。关于各时间点的肽浓度,将以刚刚添加后作为100而算出的残留率(%)对添加后时间作图(图3)。

结果

大鼠血浆中(冰上)的稳定性试验的结果,2-44在添加后30分钟的时间点为定量下限(0.5μg/mL)以下。另一方面可以确认:与2-44相比,肽-3和肽-6的任意一种均稳定。另外,观察到肽-3和肽-6的稳定性是同等的(图3)。

产业实用性

本发明的肽、其衍生物、它们的药学上可接受的盐或者它们的溶剂合物可用于再生医疗领域。

<110> 盐野义制药株式会社

GENOMIX株式会社

<120> 用于诱导组织再生的肽及其应用

<130> 18-010-PCTJP

<150> JP 2017-085793

<151> 2017-04-25

<160> 403

<170> PatentIn version 3.5

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<210> 67

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 67

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Glu Cys

35 40

<210> 68

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 68

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Glu Asp

35 40

<210> 69

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 69

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Glu Glu

35 40

<210> 70

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 70

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Glu Phe

35 40

<210> 71

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 71

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Glu Gly

35 40

<210> 72

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 72

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Glu His

35 40

<210> 73

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 73

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Glu Ile

35 40

<210> 74

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 74

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Glu Lys

35 40

<210> 75

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 75

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Glu Leu

35 40

<210> 76

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 76

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Glu Met

35 40

<210> 77

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 77

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Glu Asn

35 40

<210> 78

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 78

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Glu Pro

35 40

<210> 79

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 79

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Glu Gln

35 40

<210> 80

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 80

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Glu Arg

35 40

<210> 81

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 81

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Glu Ser

35 40

<210> 82

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 82

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Glu Thr

35 40

<210> 83

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 83

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Glu Val

35 40

<210> 84

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 84

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Glu Trp

35 40

<210> 85

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 85

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Glu Tyr

35 40

<210> 86

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 86

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Phe Ala

35 40

<210> 87

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 87

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Phe Cys

35 40

<210> 88

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 88

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Phe Asp

35 40

<210> 89

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 89

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Phe Glu

35 40

<210> 90

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 90

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Phe Phe

35 40

<210> 91

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 91

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Phe Gly

35 40

<210> 92

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 92

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Phe His

35 40

<210> 93

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 93

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Phe Ile

35 40

<210> 94

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 94

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Phe Lys

35 40

<210> 95

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 95

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Phe Leu

35 40

<210> 96

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 96

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Phe Met

35 40

<210> 97

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 97

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Phe Asn

35 40

<210> 98

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 98

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Phe Pro

35 40

<210> 99

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 99

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Phe Gln

35 40

<210> 100

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 100

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Phe Arg

35 40

<210> 101

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 101

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Phe Ser

35 40

<210> 102

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 102

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Phe Thr

35 40

<210> 103

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 103

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Phe Val

35 40

<210> 104

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 104

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Phe Trp

35 40

<210> 105

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 105

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Phe Tyr

35 40

<210> 106

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 106

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gly Ala

35 40

<210> 107

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 107

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gly Cys

35 40

<210> 108

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 108

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gly Asp

35 40

<210> 109

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 109

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gly Glu

35 40

<210> 110

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 110

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gly Phe

35 40

<210> 111

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 111

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gly Gly

35 40

<210> 112

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 112

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gly His

35 40

<210> 113

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 113

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gly Ile

35 40

<210> 114

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 114

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gly Lys

35 40

<210> 115

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 115

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gly Leu

35 40

<210> 116

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 116

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gly Met

35 40

<210> 117

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 117

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gly Asn

35 40

<210> 118

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 118

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gly Pro

35 40

<210> 119

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 119

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gly Gln

35 40

<210> 120

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 120

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gly Arg

35 40

<210> 121

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 121

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gly Ser

35 40

<210> 122

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 122

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gly Thr

35 40

<210> 123

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 123

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gly Val

35 40

<210> 124

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 124

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gly Trp

35 40

<210> 125

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 125

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gly Tyr

35 40

<210> 126

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 126

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser His Ala

35 40

<210> 127

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 127

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser His Cys

35 40

<210> 128

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 128

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser His Asp

35 40

<210> 129

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 129

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser His Glu

35 40

<210> 130

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 130

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser His Phe

35 40

<210> 131

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 131

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser His Gly

35 40

<210> 132

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 132

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser His His

35 40

<210> 133

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 133

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser His Ile

35 40

<210> 134

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 134

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser His Lys

35 40

<210> 135

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 135

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser His Leu

35 40

<210> 136

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 136

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser His Met

35 40

<210> 137

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 137

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser His Asn

35 40

<210> 138

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 138

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser His Pro

35 40

<210> 139

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 139

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser His Gln

35 40

<210> 140

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 140

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser His Arg

35 40

<210> 141

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 141

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser His Ser

35 40

<210> 142

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 142

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser His Thr

35 40

<210> 143

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 143

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser His Val

35 40

<210> 144

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 144

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser His Trp

35 40

<210> 145

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 145

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser His Tyr

35 40

<210> 146

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 146

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ile Ala

35 40

<210> 147

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 147

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ile Cys

35 40

<210> 148

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 148

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ile Asp

35 40

<210> 149

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 149

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ile Glu

35 40

<210> 150

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 150

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ile Phe

35 40

<210> 151

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 151

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ile Gly

35 40

<210> 152

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 152

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ile His

35 40

<210> 153

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 153

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ile Ile

35 40

<210> 154

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 154

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ile Lys

35 40

<210> 155

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 155

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ile Leu

35 40

<210> 156

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 156

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ile Met

35 40

<210> 157

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 157

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ile Asn

35 40

<210> 158

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 158

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ile Pro

35 40

<210> 159

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 159

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ile Gln

35 40

<210> 160

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 160

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ile Arg

35 40

<210> 161

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 161

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ile Ser

35 40

<210> 162

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 162

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ile Thr

35 40

<210> 163

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 163

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ile Val

35 40

<210> 164

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 164

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ile Trp

35 40

<210> 165

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 165

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ile Tyr

35 40

<210> 166

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 166

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Cys

35 40

<210> 167

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 167

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Asp

35 40

<210> 168

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 168

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Phe

35 40

<210> 169

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 169

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Gly

35 40

<210> 170

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 170

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys His

35 40

<210> 171

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 171

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Ile

35 40

<210> 172

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 172

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Leu

35 40

<210> 173

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 173

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Met

35 40

<210> 174

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 174

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Asn

35 40

<210> 175

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 175

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Gln

35 40

<210> 176

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 176

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Arg

35 40

<210> 177

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 177

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Ser

35 40

<210> 178

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 178

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Thr

35 40

<210> 179

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 179

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Val

35 40

<210> 180

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 180

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Trp

35 40

<210> 181

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 181

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Tyr

35 40

<210> 182

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 182

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Leu Ala

35 40

<210> 183

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 183

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Leu Cys

35 40

<210> 184

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 184

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Leu Asp

35 40

<210> 185

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 185

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Leu Glu

35 40

<210> 186

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 186

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Leu Phe

35 40

<210> 187

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 187

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Leu Gly

35 40

<210> 188

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 188

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Leu His

35 40

<210> 189

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 189

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Leu Ile

35 40

<210> 190

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 190

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Leu Lys

35 40

<210> 191

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 191

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Leu Leu

35 40

<210> 192

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 192

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Leu Met

35 40

<210> 193

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 193

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Leu Asn

35 40

<210> 194

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 194

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Leu Pro

35 40

<210> 195

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 195

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Leu Gln

35 40

<210> 196

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 196

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Leu Arg

35 40

<210> 197

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 197

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Leu Ser

35 40

<210> 198

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 198

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Leu Thr

35 40

<210> 199

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 199

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Leu Val

35 40

<210> 200

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 200

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Leu Trp

35 40

<210> 201

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 201

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Leu Tyr

35 40

<210> 202

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 202

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Met Ala

35 40

<210> 203

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 203

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Met Cys

35 40

<210> 204

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 204

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Met Asp

35 40

<210> 205

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 205

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Met Glu

35 40

<210> 206

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 206

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Met Phe

35 40

<210> 207

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 207

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Met Gly

35 40

<210> 208

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 208

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Met His

35 40

<210> 209

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 209

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Met Ile

35 40

<210> 210

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 210

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Met Lys

35 40

<210> 211

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 211

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Met Leu

35 40

<210> 212

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 212

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Met Met

35 40

<210> 213

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 213

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Met Asn

35 40

<210> 214

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 214

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Met Pro

35 40

<210> 215

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 215

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Met Gln

35 40

<210> 216

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 216

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Met Arg

35 40

<210> 217

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 217

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Met Ser

35 40

<210> 218

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 218

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Met Thr

35 40

<210> 219

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 219

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Met Val

35 40

<210> 220

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 220

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Met Trp

35 40

<210> 221

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 221

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Met Tyr

35 40

<210> 222

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 222

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Asn Ala

35 40

<210> 223

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 223

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Asn Cys

35 40

<210> 224

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 224

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Asn Asp

35 40

<210> 225

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 225

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Asn Glu

35 40

<210> 226

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 226

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Asn Phe

35 40

<210> 227

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 227

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Asn Gly

35 40

<210> 228

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 228

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Asn His

35 40

<210> 229

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 229

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Asn Ile

35 40

<210> 230

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 230

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Asn Lys

35 40

<210> 231

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 231

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Asn Leu

35 40

<210> 232

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 232

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Asn Met

35 40

<210> 233

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 233

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Asn Asn

35 40

<210> 234

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 234

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Asn Pro

35 40

<210> 235

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 235

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Asn Gln

35 40

<210> 236

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 236

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Asn Arg

35 40

<210> 237

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 237

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Asn Ser

35 40

<210> 238

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 238

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Asn Thr

35 40

<210> 239

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 239

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Asn Val

35 40

<210> 240

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 240

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Asn Trp

35 40

<210> 241

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 241

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Asn Tyr

35 40

<210> 242

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 242

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Pro Ala

35 40

<210> 243

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 243

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Pro Cys

35 40

<210> 244

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 244

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Pro Asp

35 40

<210> 245

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 245

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Pro Glu

35 40

<210> 246

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 246

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Pro Phe

35 40

<210> 247

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 247

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Pro Gly

35 40

<210> 248

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 248

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Pro His

35 40

<210> 249

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 249

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Pro Ile

35 40

<210> 250

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 250

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Pro Leu

35 40

<210> 251

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 251

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Pro Met

35 40

<210> 252

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 252

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Pro Asn

35 40

<210> 253

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 253

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Pro Gln

35 40

<210> 254

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 254

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Pro Arg

35 40

<210> 255

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 255

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Pro Ser

35 40

<210> 256

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 256

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Pro Thr

35 40

<210> 257

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 257

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Pro Val

35 40

<210> 258

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 258

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Pro Trp

35 40

<210> 259

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 259

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Pro Tyr

35 40

<210> 260

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 260

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gln Ala

35 40

<210> 261

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 261

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gln Cys

35 40

<210> 262

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 262

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gln Asp

35 40

<210> 263

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 263

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gln Glu

35 40

<210> 264

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 264

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gln Phe

35 40

<210> 265

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 265

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gln Gly

35 40

<210> 266

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 266

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gln His

35 40

<210> 267

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 267

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gln Ile

35 40

<210> 268

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 268

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gln Lys

35 40

<210> 269

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 269

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gln Leu

35 40

<210> 270

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 270

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gln Met

35 40

<210> 271

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 271

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gln Asn

35 40

<210> 272

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 272

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gln Pro

35 40

<210> 273

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 273

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gln Gln

35 40

<210> 274

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 274

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gln Arg

35 40

<210> 275

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 275

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gln Ser

35 40

<210> 276

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 276

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gln Thr

35 40

<210> 277

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 277

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gln Val

35 40

<210> 278

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 278

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gln Trp

35 40

<210> 279

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 279

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Gln Tyr

35 40

<210> 280

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 280

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Arg Ala

35 40

<210> 281

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 281

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Arg Cys

35 40

<210> 282

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 282

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Arg Asp

35 40

<210> 283

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 283

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Arg Glu

35 40

<210> 284

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 284

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Arg Phe

35 40

<210> 285

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 285

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Arg Gly

35 40

<210> 286

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 286

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Arg His

35 40

<210> 287

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 287

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Arg Ile

35 40

<210> 288

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 288

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Arg Lys

35 40

<210> 289

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 289

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Arg Leu

35 40

<210> 290

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 290

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Arg Met

35 40

<210> 291

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 291

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Arg Asn

35 40

<210> 292

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 292

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Arg Pro

35 40

<210> 293

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 293

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Arg Gln

35 40

<210> 294

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 294

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Arg Arg

35 40

<210> 295

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 295

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Arg Ser

35 40

<210> 296

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 296

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Arg Thr

35 40

<210> 297

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 297

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Arg Val

35 40

<210> 298

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 298

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Arg Trp

35 40

<210> 299

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 299

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Arg Tyr

35 40

<210> 300

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 300

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ser Ala

35 40

<210> 301

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 301

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ser Cys

35 40

<210> 302

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 302

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ser Asp

35 40

<210> 303

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 303

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ser Glu

35 40

<210> 304

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 304

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ser Phe

35 40

<210> 305

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 305

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ser Gly

35 40

<210> 306

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 306

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ser His

35 40

<210> 307

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 307

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ser Ile

35 40

<210> 308

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 308

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ser Lys

35 40

<210> 309

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 309

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ser Leu

35 40

<210> 310

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 310

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ser Met

35 40

<210> 311

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 311

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ser Asn

35 40

<210> 312

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 312

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ser Pro

35 40

<210> 313

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 313

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ser Gln

35 40

<210> 314

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 314

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ser Arg

35 40

<210> 315

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 315

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ser Ser

35 40

<210> 316

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 316

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ser Thr

35 40

<210> 317

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 317

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ser Val

35 40

<210> 318

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 318

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ser Trp

35 40

<210> 319

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 319

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Ser Tyr

35 40

<210> 320

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 320

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Thr Ala

35 40

<210> 321

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 321

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Thr Cys

35 40

<210> 322

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 322

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Thr Asp

35 40

<210> 323

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 323

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Thr Glu

35 40

<210> 324

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 324

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Thr Phe

35 40

<210> 325

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 325

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Thr Gly

35 40

<210> 326

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 326

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Thr His

35 40

<210> 327

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 327

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Thr Ile

35 40

<210> 328

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 328

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Thr Lys

35 40

<210> 329

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 329

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Thr Leu

35 40

<210> 330

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 330

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Thr Met

35 40

<210> 331

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 331

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Thr Asn

35 40

<210> 332

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 332

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Thr Pro

35 40

<210> 333

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 333

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Thr Gln

35 40

<210> 334

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 334

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Thr Arg

35 40

<210> 335

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 335

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Thr Ser

35 40

<210> 336

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 336

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Thr Thr

35 40

<210> 337

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 337

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Thr Val

35 40

<210> 338

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 338

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Thr Trp

35 40

<210> 339

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 339

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Thr Tyr

35 40

<210> 340

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 340

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Val Ala

35 40

<210> 341

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 341

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Val Cys

35 40

<210> 342

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 342

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Val Asp

35 40

<210> 343

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 343

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Val Glu

35 40

<210> 344

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 344

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Val Phe

35 40

<210> 345

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 345

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Val Gly

35 40

<210> 346

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 346

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Val His

35 40

<210> 347

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 347

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Val Ile

35 40

<210> 348

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 348

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Val Lys

35 40

<210> 349

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 349

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Val Leu

35 40

<210> 350

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 350

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Val Met

35 40

<210> 351

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 351

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Val Asn

35 40

<210> 352

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 352

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Val Pro

35 40

<210> 353

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 353

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Val Gln

35 40

<210> 354

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 354

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Val Arg

35 40

<210> 355

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 355

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Val Ser

35 40

<210> 356

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 356

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Val Thr

35 40

<210> 357

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 357

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Val Val

35 40

<210> 358

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 358

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Val Trp

35 40

<210> 359

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 359

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Val Tyr

35 40

<210> 360

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 360

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Trp Ala

35 40

<210> 361

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 361

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Trp Cys

35 40

<210> 362

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 362

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Trp Asp

35 40

<210> 363

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 363

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Trp Glu

35 40

<210> 364

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 364

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Trp Phe

35 40

<210> 365

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 365

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Trp Gly

35 40

<210> 366

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 366

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Trp His

35 40

<210> 367

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 367

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Trp Ile

35 40

<210> 368

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 368

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Trp Lys

35 40

<210> 369

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 369

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Trp Leu

35 40

<210> 370

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 370

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Trp Met

35 40

<210> 371

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 371

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Trp Asn

35 40

<210> 372

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 372

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Trp Pro

35 40

<210> 373

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 373

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Trp Gln

35 40

<210> 374

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 374

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Trp Arg

35 40

<210> 375

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 375

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Trp Ser

35 40

<210> 376

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 376

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Trp Thr

35 40

<210> 377

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 377

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Trp Val

35 40

<210> 378

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 378

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Trp Trp

35 40

<210> 379

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 379

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Trp Tyr

35 40

<210> 380

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 380

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Tyr Ala

35 40

<210> 381

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 381

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Tyr Cys

35 40

<210> 382

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 382

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Tyr Asp

35 40

<210> 383

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 383

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Tyr Glu

35 40

<210> 384

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 384

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Tyr Phe

35 40

<210> 385

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 385

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Tyr Gly

35 40

<210> 386

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 386

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Tyr His

35 40

<210> 387

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 387

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Tyr Ile

35 40

<210> 388

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 388

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Tyr Lys

35 40

<210> 389

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 389

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Tyr Leu

35 40

<210> 390

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 390

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Tyr Met

35 40

<210> 391

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 391

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Tyr Asn

35 40

<210> 392

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 392

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Tyr Pro

35 40

<210> 393

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 393

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Tyr Gln

35 40

<210> 394

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 394

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Tyr Arg

35 40

<210> 395

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 395

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Tyr Ser

35 40

<210> 396

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 396

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Tyr Thr

35 40

<210> 397

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 397

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Tyr Val

35 40

<210> 398

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 398

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Tyr Trp

35 40

<210> 399

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 399

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Tyr Tyr

35 40

<210> 400

<211> 43

<212> PRT

<213> 人工序列

<220>

<223>

<400> 400

Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr Ala

1 5 10 15

Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro Asp

20 25 30

Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys

35 40

<210> 401

<211> 215

<212> PRT

<213> Homo sapiens

<400> 401

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys Cys Ser Glu Arg

35 40 45

Trp Lys Thr Met Ser Ala Lys Glu Lys Gly Lys Phe Glu Asp Met Ala

50 55 60

Lys Ala Asp Lys Ala Arg Tyr Glu Arg Glu Met Lys Thr Tyr Ile Pro

65 70 75 80

Pro Lys Gly Glu Thr Lys Lys Lys Phe Lys Asp Pro Asn Ala Pro Lys

85 90 95

Arg Pro Pro Ser Ala Phe Phe Leu Phe Cys Ser Glu Tyr Arg Pro Lys

100 105 110

Ile Lys Gly Glu His Pro Gly Leu Ser Ile Gly Asp Val Ala Lys Lys

115 120 125

Leu Gly Glu Met Trp Asn Asn Thr Ala Ala Asp Asp Lys Gln Pro Tyr

130 135 140

Glu Lys Lys Ala Ala Lys Leu Lys Glu Lys Tyr Glu Lys Asp Ile Ala

145 150 155 160

Ala Tyr Arg Ala Lys Gly Lys Pro Asp Ala Ala Lys Lys Gly Val Val

165 170 175

Lys Ala Glu Lys Ser Lys Lys Lys Lys Glu Glu Glu Glu Asp Glu Glu

180 185 190

Asp Glu Glu Asp Glu Glu Glu Glu Glu Asp Glu Glu Asp Glu Asp Glu

195 200 205

Glu Glu Asp Asp Asp Asp Asp

210 215

<210> 402

<211> 44

<212> PRT

<213> 人工序列

<220>

<223>

<400> 402

Met Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr

1 5 10 15

Ala Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro

20 25 30

Asp Ala Ser Val Asn Phe Ser Glu Phe Ser Lys Lys

35 40

<210> 403

<211> 43

<212> PRT

<213> 人工序列

<220>

<223>

<400> 403

Gly Lys Gly Asp Pro Lys Lys Pro Arg Gly Lys Met Ser Ser Tyr Ala

1 5 10 15

Phe Phe Val Gln Thr Cys Arg Glu Glu His Lys Lys Lys His Pro Asp

20 25 30

Ala Ser Val Asn Phe Ser Glu Phe Ser Pro Pro

35 40

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