阅读说明：本技术 特异性肽网格蛋白抑制剂 (Specific peptide clathrin inhibitors ) 是由 奥列格·阿尔卡季耶维奇·科京 阿尔卡季·米哈伊洛维奇·科京 马克西姆·奥列戈维奇·叶梅利亚诺夫 于 2018-03-01 设计创作，主要内容包括：本发明涉及化学和制药工业。提出了使用合成肽作为特异性的网格蛋白抑制剂。还提出了一种预防或治疗动物疾病或病症的方法,包括给予有效量的肽或前药或上述肽的生理上可接受的盐或溶剂化物,或包含上述肽作为特异性的网格蛋白抑制剂的药物组合物。该肽可用于医学、兽医学和药理学,以创造新的作为特定的网格蛋白抑制剂的药物。(The present invention relates to the chemical and pharmaceutical industries. The use of synthetic peptides as specific clathrin inhibitors has been proposed. Also provided is a method of preventing or treating a disease or condition in an animal comprising administering an effective amount of a peptide or prodrug or a physiologically acceptable salt or solvate of the peptide, or a pharmaceutical composition comprising the peptide as a specific clathrin inhibitor. The peptides can be used in medicine, veterinary medicine and pharmacology to create new drugs that are specific clathrin inhibitors.)

1. General formula (I) [ SEQ ID NO:1] use of synthetic peptides

XDL-XDL1-XDL2-L-Lys-L-Leu-XDL3-L-Thr-R2(I), wherein:

XDL-absent amino acid or L-Tyr,

XDL 1-one of the following amino acids: L-Leu, L-Ala or D-Ala,

XDL 2-one of the following amino acids: L-His, D-His, L-Ala or D-Ala,

XDL 3-one of the following amino acids: L-Gln, L-Ala or D-Ala;

R2-OMe or NH₂，

Or a peptide-reversal of general formula (I) with an inverted amino acid sequence, wherein the L-form amino acid is replaced with a D-form amino acid and the D-form amino acid is replaced with an L-form amino acid, i.e. general formula (II) [ SEQ ID NO:2]

D-Thr-XDL4-D-Leu-D-Lys-XDL5-XDL6-XDL7-R2 (II) wherein:

XDL 4-one of the following amino acids: D-Gln, D-Ala or L-Ala;

XDL 5-one of the following amino acids: D-His, L-His, D-Ala or L-Ala,

XDL 6-one of the following amino acids: D-Leu, D-Ala or L-Ala,

XDL 7-with no amino acid present or D-Tyr,

R2-OMe or NH₂，

As a specific inhibitor of clathrin.

2. A method for preventing or treating a disease or condition in an animal comprising administering an effective amount of a peptide of general formula (I) [ SEQ ID NO:1] or general formula (II) [ SEQ ID NO:2] or a synthetic peptide or a prodrug thereof, or a physiologically acceptable salt or solvate of said peptide, or a pharmaceutical composition comprising said peptide as a specific inhibitor of clathrin.

Example 1 peptide L-Leu-D-His-L-Lys-L-Leu-Lln-Lln-Thr-NH₂(peptide No. 7, SEQ ID NO: 1)

The peptide L-Leu-D-His-L-Lys-L-Leu-L-Gln-L-Thr-NH was prepared by automated solid phase synthesis of Fmoc-Rink protocol using the DCC/HOBt (N, N' -dicyclohexylcarbodiimide/1-hydroxybenzotriazole) method on polymer (Rink Amide resin, 0.6mmol amino groups per 1 g resin)₂And amino acid activation is performed. Deprotection was performed by treatment with piperidine/DMF solution (piperidine/N, N-dimethylformamide) (1:4) for 7 min. The protecting groups of the side chains give rise to the following groups: tBu (tert-butyl ether) for tyrosine, threonine, Trt (tri) for glutamine and histidineBenzyl or trityl), Boc (tert-butyloxycarbonyl) lysine. Cleavage of the peptide from the resin and use of TFA/H₂A mixture of O/EDT (trifluoroacetic acid/water/1, 2-ethanedithiol) (90:5:5) was deprotected. Purification of the peptide was performed by reverse phase HPLC (C18 column), eluent acetonitrile-water (containing 0.1M potassium dihydrogen phosphate) in a ratio of 6: 4. The peptides were characterized using a mass spectrometer. The peptide purity was checked by HPLC using a column Waters Delta PakC18, 3.9X 150mm 5 μmSolution A: 0.1% TFA in 100% water/MeCN; the flow rate is-1 mL/min; the detection wavelength was-230 nm (FIG. 1).