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Application of a polypeptide or its derivatives in the treatment of hypertensive cardiac hypertrophy

A technology for myocardial hypertrophy and hypertension, applied in the field of medicine, can solve the problems of lack of kinase activity, lack of ATP binding sites and catalytic residues, etc., and achieve significant curative effect

Active Publication Date: 2020-07-14
INST OF MATERIA MEDICA CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

All three proteins contain Ser / Thr protein kinase-like domains (Kinaselike domain, KD), but lack ATP binding sites and catalytic residues, so there is no kinase activity

Method used

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  • Application of a polypeptide or its derivatives in the treatment of hypertensive cardiac hypertrophy
  • Application of a polypeptide or its derivatives in the treatment of hypertensive cardiac hypertrophy
  • Application of a polypeptide or its derivatives in the treatment of hypertensive cardiac hypertrophy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0058] Example 1: Screening of peptides binding to TRB3 protein and identification of their biological functions.

[0059] The specific screening method and identification of peptides that bind to TRB3 protein refer to the patent: Peptides that specifically bind to TRB3 protein, its screening method, identification and use (invention title), application number: 201310206907.9. details as follows:

[0060] (1) Use surface plasmon resonance to screen peptides that bind to TRB3 protein.

[0061] First, the P62 protein is truncated into different polypeptide fragments, and the peptides are synthesized with a peptide solid-phase synthesizer. This process is carried out by Beijing Saibaisheng Gene Co., Ltd. EXAMPLES The entire screening process was carried out in a surface plasmon resonance instrument BiacoreT200.

[0062] The screening method is as follows:

[0063] (1) The purified protein TRB3 (purchased from R&D Company) was coupled to a CM5 chip (purchased from GE Company) t...

Embodiment 2

[0078] Example 2: Establishment and evaluation of a mouse model of hypertensive cardiac hypertrophy.

[0079] (1) Establishment of mouse model of hypertensive cardiac hypertrophy

[0080]SPF grade ICR mice (male, 7-8 weeks old) were purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd., and were raised in the Experimental Animal Center of the Institute of Materia Medica, Chinese Academy of Medical Sciences, with constant temperature and humidity, and free diet. After the mice were bred adaptively for one week, the ICR mice were anesthetized by intraperitoneal injection of 4% chloral hydrate 10ml / kg, opened the abdomen under sterile conditions, separated the abdominal aorta, and used No. Tighten it together with an injection needle with an outer diameter of 0.6mm, remove the needle quickly, and suture the abdomen layer by layer. The sham operation (sham) group did not perform silk ligation, and other treatments were the same. After 30 days of normal fe...

Embodiment 3

[0120] Example 3: Administration of Pep2-A2 to treat hypertensive cardiac hypertrophy in mice.

[0121] See Example 2 for the establishment and evaluation of the mouse model of hypertensive cardiac hypertrophy. This example is based on the mouse model established in Example 2. After being treated with Pep2-A2, the therapeutic effect is tested.

[0122] (1) Pep2-A2 treatment reduces the mortality rate of mice with hypertensive cardiac hypertrophy.

[0123] The specific operation steps are as follows:

[0124] SPF grade ICR mice (male, 7-8 weeks old) were purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd., and were raised in the Experimental Animal Center of the Institute of Materia Medica, Chinese Academy of Medical Sciences, with constant temperature and humidity, and free diet. After one week of adaptive feeding, the mice were randomly divided into 3 groups according to body weight: 20 mice in the control group, 20 mice in the abdominal aorta ligat...

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Abstract

The invention discloses application of a polypeptide able to specifically bind TRB3 or polypeptide derivative or polypeptide chimeric peptide in preparation of drugs or vaccines for prevention and / or treatment of hypertensive myocardial hypertrophy. The polypeptide has an amino acid sequence shown as SEQ ID NO:1, the amino acid sequence of the polypeptide derivative is a SEQ ID NO:1 derived amino acid sequence that is obtained by subjecting the amino acid sequence shown as SEQ ID NO:1 to substitution, deletion or adding by one or several amino acid residues and has the same activity to an amino acid residue sequence of SEQ ID NO:1, and the polypeptide chimeric peptide is formed by connecting the polypeptide or polypeptide derivative with a cell-penetrating peptide. The invention also further discloses a nucleotide fragment encoding the polypeptide or polypeptide derivative, and application of pharmaceutical compositions containing the polypeptide or polypeptide derivative or polypeptide chimeric peptide and the nucleotide sequence thereof in preparation of drugs or vaccines for prevention and / or treatment of hypertensive myocardial hypertrophy.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to the application of a polypeptide or a polypeptide derivative or a polypeptide chimeric peptide in the preparation of drugs or vaccines for preventing and / or treating hypertensive cardiac hypertrophy. Background technique [0002] Myocardial hypertrophy is the initial physiological adaptive response to elevated blood pressure and increased afterload, and is also a common pathophysiological process of many cardiovascular diseases, such as hypertension, myocardial infarction, valvular heart disease, and cardiomyopathy. Although blood pressure can be controlled in the normal range through drug intervention, myocardial hypertrophy will inevitably gradually progress to chronic heart failure. In fact, myocardial hypertrophy is an independent risk factor for cardiovascular disease, which doubles the mortality rate of cardiovascular disease. The treatment of myocardial hypertrophy is stil...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K38/08A61K38/10A61K38/16A61K39/00A61K48/00A61P9/00A61P9/12
CPCA61K38/08A61K38/10A61K38/16A61K39/0005A61K48/005A61K2039/53
Inventor 胡卓伟林珩刘晓波李珂花芳
Owner INST OF MATERIA MEDICA CHINESE ACAD OF MEDICAL SCI
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