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Angiogenesis agonist polypeptide and application

An angiogenesis and agonist technology, applied in the field of medicine, can solve the problems of drug resistance, antibody neutralization, large molecular weight, etc., and achieve the effect of treating ischemic diseases

Inactive Publication Date: 2016-09-28
NANJING MEDICAL UNIV AFFILIATED BRAIN HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Despite this, there are currently no studies on the direct use of sTEM5 in the treatment of ischemic diseases, including stroke
Moreover, the soluble TEM5 (sTEM5) detached from GPR124 has a relatively large molecular weight, short-term exposure can induce immune allergy, and long-term exposure can cause antibody neutralization, resulting in drug resistance

Method used

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  • Angiogenesis agonist polypeptide and application
  • Angiogenesis agonist polypeptide and application
  • Angiogenesis agonist polypeptide and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0017] Chemical synthesis of peptides

[0018] The peptides are synthesized by solid-phase chemical synthesis (synthesized by Karebay Biochem), and purified by high performance liquid chromatography to obtain the peptides. Using mass spectrometry such as figure 1 , Its amino acid sequence is SEQ ID NO:1. The purity of the polypeptide was determined by the RP-HPLC method, and the result showed that the degree of the polypeptide obtained in Example 1 was 97.95%, which met the design requirements. Chromatogram such as figure 2 .

Embodiment 2

[0020] The result of peptide docking with receptor molecule

[0021] The molecular docking function module of molecular docking software is used to evaluate the degree of docking between the peptide and the receptor molecule. Methods: (1) Receptor preparation: retrieve the PDB number of the corresponding protein receptor from Brookheaven protein crystal structure database (http: / / www.rcsb.org / pdb / ); (2) Ligand preparation: analyze GPR124 Different functional areas of cell membrane surface receptors; According to different functional areas, the amino acid sequence of SEQ ID NO:1 is truncated from the GPR124 sequence protein, which is used as the ligand structure; (3) Molecular docking: select the C-score option and run docking, function scoring.

[0022] The evaluation and scoring results showed that the total-score value of the binding between the polypeptide of Example 1 and the specific receptor was 11.2391. The specific binding requirement that meets the software regulations i...

Embodiment 3

[0024] The scratch test was used to evaluate the effect of peptides on the migration of vascular endothelial cells. First use a marker pen on the back of the 24-well plate, compare it with a straightedge, and draw evenly horizontal lines, about every 0.5cm, across the holes. Each hole passes through 3 lines; HUVEC cells grown in log numbers are measured at 2.0×10 5 Pieces / well were added to a 24-well culture plate and cultured for 24h. On the second day, use a 10μl pipette tip to compare with a ruler, and make a scratch perpendicular to the horizontal line on the back. The intersection of the scratch and the horizontal line on the back is the fixed observation site; the experiment hole and the positive drug control hole are respectively added with different concentrations of experiment Drug angiogenesis agonist polypeptide and positive control polypeptide sTEM5; the blank group is added with the same volume of solvent, and each hole is set with five multiple holes; put in 37℃, ...

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PUM

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Abstract

The invention relates to the field of medicine, in particular to angiogenesis agonist polypeptide, namely, polypeptide capable of treating ischemic diseases. The angiogenesis agonist polypeptide is characterized in that the sequence of the polypeptide is a brand-new sequence, and the angiogenesis agonist polypeptide has the function of promoting angiogenesis. The angiogenesis agonist polypeptide is used for cerebral arterial thrombosis. The angiogenesis agonist polypeptide has the advantages that the angiogenesis agonist polypeptide is novel micro-molecule polypeptide screened out of cytomembrane surface receptor sequence protein which has the sequence of GPR124 and has angiogenesis activity, the polypeptide sequence can combine specificity and integrin, adhesion and transfer of cells in the angiogenesis process are adjusted, and therefore the function of treating the ischemic disease is achieved. Potential new medicine development value is achieved.

Description

Technical field: [0001] The present invention relates to the field of medicine, in particular to an angiogenesis agonist polypeptide medicine for treating cardiovascular and cerebrovascular diseases. Background technique: [0002] Angiogenesis refers to the formation of new blood vessels from existing capillaries or post-capillary veins. It mainly includes: degradation of vascular basement membrane in the activation phase; activation, proliferation, and migration of vascular endothelial cells; reconstruction to form new blood vessels And the vascular network is a complex process involving many kinds of cells and many kinds of molecules. Angiogenesis is a complex process in which pro-angiogenic factors and inhibitors coordinate their actions. Normally, the two are in a balanced state. Once this balance is broken, the vascular system will be activated, causing excessive angiogenesis or inhibiting the vascular system to degenerate blood vessels. Angiogenesis is the process of gener...

Claims

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Application Information

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IPC IPC(8): C07K14/705A61K38/17A61P9/10A61P9/00
CPCC07K14/705A61K38/00
Inventor 肖红沈鸿李瑞
Owner NANJING MEDICAL UNIV AFFILIATED BRAIN HOSPITAL
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