阅读说明：本技术 多肽及其应用和dpp-ⅳ抑制剂或降血糖药物或保健品 (Polypeptide and application thereof, and DPP-IV inhibitor or hypoglycemic drug or health product ) 是由 靳艳 叶明亮 晏嘉泽 于 2018-07-27 设计创作，主要内容包括：本发明涉及抑制二肽基肽酶(DPP-Ⅳ,dipeptidyl peptidaseⅣ)活性及降血糖的一种多肽化合物Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala,它的氨基酸序列为Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala。多肽Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala具有DPP-Ⅳ抑制活性及降血糖活性,作为降血糖以及治疗II型糖尿病的保健品和药物先导化合物具有良好的应用前景。(The invention relates to a polypeptide compound Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala for inhibiting the activity of dipeptidyl peptidase IV (DPP-IV) and reducing blood sugar, and the amino acid sequence of the polypeptide compound is Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala. The polypeptide Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala has DPP-IV inhibitory activity and hypoglycemic activity, and has good application prospect as a health product and a medicine lead compound for reducing blood sugar and treating type II diabetes.)

1. A polypeptide, characterized by: the polypeptide is Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala and has a sequence table SEQ ID NO: 1, amino acid sequence; the amino acid sequence of the polypeptide is Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala.

2. The use according to claim 1 for the preparation of DPP-iv inhibitors or hypoglycemic drugs or nutraceuticals or drugs or nutraceuticals for the treatment of type II diabetes.

3. Use according to claim 2, characterized in that: the DPP-IV inhibitor and/or the hypoglycemic drug take polypeptide Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala as an active ingredient.

4. Use according to claim 2, characterized in that: the DPP-IV inhibitor, the hypoglycemic drug or the health care product, or the drug or the health care product for treating type II diabetes can be added with a pharmaceutically acceptable carrier or auxiliary material.

5. A DPP-IV inhibitor, or a hypoglycemic drug or health product, or a drug or health product for treating type II diabetes mellitus, is characterized in that: the DPP-IV inhibitor or hypoglycemic drug takes the polypeptide Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala as the active ingredient in claim 1.

6. The DPP-iv inhibitor, or a hypoglycemic drug or health product, or a drug or health product for the treatment of type II diabetes according to claim 5, characterized in that: the DPP-IV inhibitor, the hypoglycemic drug or the health care product, or the drug or the health care product for treating type II diabetes can be added with a pharmaceutically acceptable carrier or auxiliary material.

Technical Field

The invention relates to application of polypeptide Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala in preparation of dipeptidyl peptidase IV (DPP-IV) inhibiting and hypoglycemic drugs and health care products.

Background

Diabetes is a syndrome of disturbances of glucose, protein, lipid metabolism due to absolute or relative insufficiency of insulin in the body. Currently, diabetes has become a global epidemic. According to the statistics of the world health organization, the incidence rate of diabetes mellitus is increasing with a certain amplitude every year. The prevalence rate of diabetes in China in 2016 is 9.6%, and with the improvement of living standard, the number still rises sharply.

Dipeptidyl peptidase IV (DPP-IV) is a serine protease whose substrate includes a polypeptide whose second position at the N-terminus is a proline or alanine residue. It can hydrolyze two amino acid residues from the N end of the peptide chain, can rapidly and effectively degrade glucagon-like peptide 1 (GLP-1), wherein GLP-1 is one of the most effective stimulators for insulin generation and secretion, so that the inhibition of DPP-IV can enhance the action of endogenous GLP-1, thereby improving the level of insulin in blood and further reducing and maintaining the blood sugar level of a diabetic patient (Bioorg Med chem.2007,15(7): 2715) 2735). Moreover, GLP-1 regulates insulin secretion and has strict blood sugar concentration dependence, and only GLP-1 can improve the insulin secretion level under the condition of hyperglycemia, so that the DPP-IV inhibitor has no risk of hypoglycemia caused by taking medicines (Best practice Res Clin endocrine Metab.2009,23(4):479-86)

Disclosure of Invention

The invention aims to provide an application and a rapid screening method of polypeptide Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala in inhibiting DPP-IV activity and reducing blood sugar; the polypeptide Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala has DPP-IV inhibitory activity and hypoglycemic activity, and has good application prospect as a health product and a medicine lead compound for hyperglycemia and type II diabetes.

In order to achieve the purpose, the polypeptide Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala is used as an effective component for inhibiting DPP-IV activity and reducing blood sugar.

It has the sequence table of SEQ ID NO: 1, amino acid sequence; the polypeptide Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala is the active component of DPP-IV inhibitor and hypoglycemic drugs and health products, wherein pharmaceutically acceptable carriers or auxiliary materials can be added.

The polypeptide Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala with DPP-IV inhibiting activity and hypoglycemic activity is derived from Cervus Nippon Temminck. Since the protein library of deer is not perfect enough and the total protein amount is small, and the homology of cattle and deer gene exceeds 90% (Sui Z G, Yuan H M, Liang Z, et al. Talanta,2013,107,189-194.), the bovine (bovine) family is selected as the protein database in the experiment. The polypeptide Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala is derived from Alpha globin chain protein of a bovine protein library, contains 11 amino acid residues, has an amino acid sequence of Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala, is in a single-chain linear structure, is white powder, is easy to dissolve in water, and has a molecular weight of 1214 Da; has better inhibiting effect on DPP-IV activity, IC ₅₀Is 108 ± 7 μ M (n ═ 3, Mean ± SD).

The polypeptide Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala possesses the characteristics required for DPP-IV inhibitors:

the DPP-IV inhibitory peptide at least comprises one Pro residue, and particularly, the DPP-IV inhibitory activity is particularly obvious when the second position at the N terminal is the Pro residue. The polypeptide Phe-Pro-His-Phe-Asp-Leu-Ser-His-Gly-Ser-Ala contains a Pro residue and is located second in the N-terminus, thus satisfying this condition for influencing activity.

Compared with the prior art, the invention has the following beneficial effects:

the invention obtains and determines the structure of the active compound from the pilose antler for the first time, and the compound has better DPP-IV inhibiting activity, so the compound has good potential and application prospect when being used as a lead compound of the medicine for treating hyperglycemia and type II diabetes.

Detailed Description