Application of integrin intracellular peptide sequences to inhibiting neovascularization

A new blood vessel, integrin technology, applied in the direction of peptide/protein components, peptides, specific peptides, etc., can solve the problem of unclear activation and regulation, and achieve the effect of inhibiting growth and inhibiting angiogenesis

Active Publication Date: 2017-10-17
SHANGHAI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, whether β3-endonexin is involved in the activation and regulation of β3-type integrins is still unclear

Method used

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  • Application of integrin intracellular peptide sequences to inhibiting neovascularization
  • Application of integrin intracellular peptide sequences to inhibiting neovascularization
  • Application of integrin intracellular peptide sequences to inhibiting neovascularization

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Example 1: Synthesis and purification of mβCTP series polypeptide molecules

[0023] For molecular nomenclature and amino acid sequences of mβCTP series derivative peptides containing target peptides, see figure 1 (A). This series of peptides were synthesized in the company, using the manual solid-phase Fmoc method, using Fmoc-Gly-Wang resin as the starting material, and synthesized from the C-terminus to the N-terminus. The HP1100 type (Agilent, USA) reversed-phase high-performance liquid chromatography was used for purification, and the purity reached 99.62%. The method is a conventional synthesis method for small molecule polypeptides.

Embodiment 2

[0024] Example 2: Experimental study on the effect of mβCTP series polypeptides on neovascularization by umbilical vein endothelial cells (HUVEC) vascular-like tube formation:

[0025] see figure 1 , Human umbilical vein endothelial cells (HUVEC) cultured in vitro can self-assemble into a tube-like structure similar to blood vessels on the basement membrane matrigel containing growth factors. Add different mβCTPs (final concentration 20 μM) to the cell culture medium to observe their ability to inhibit the assembly pipeline of HUVEC cells. see figure 1 (C-D), the results showed that, compared with the no-drug treatment group, the addition of derivative peptides mβ3CTP, mβ5CTP, and mβ6CTP could effectively inhibit the formation of pipelines, indicating that these polypeptides had a significant inhibitory effect on the formation of blood vessel-like pipeline structures in HUVEC cells in vitro. At the same time, the experimental results also indicate that the inhibitory functio...

Embodiment 3

[0027] Example 3: Experiment of blood vessel formation in basement membrane matrix in mice:

[0028] see figure 2 , the experimental materials were nude mice (BALB / C), 6 weeks old, male (7 nude mice in each group), basement membrane matrigel (Matrigel). After the basement membrane matrigel was melted on ice, 600ng / ml bFGF, 100U / mlheparin and different mβCTP polypeptides (50μM) were added. Then 500 μl of basement membrane-matrigel mixture was injected subcutaneously in nude mice. The basement membrane matrigel enters the mouse body and solidifies rapidly and induces the growth of new blood vessels. After 7 days, the solid Matrigel block is carefully peeled off from the mouse skin to measure the content of hemoglobin in the basement membrane matrigel; at the same time, the fixed basement membrane Matrigel was subjected to histochemical analysis (HE staining). The results showed that in the matrix with the same weight, the content of hemoglobin in the mβ3CTP, mβ5CTP, and mβ6C...

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Abstract

The invention relates to a series of peptide compounds containing integrin conserved sequences and having a function of inhibiting in vitro and vivo neovascularization. The functional peptide compounds have amino acid sequences shown as the first item of claims. The micromolecular peptide compounds can be coupled to cell-penetrating peptides to enter cells and then be combined with common signaling protein molecules to inhibit neovascularization and to achieve the effect of inhibiting in vivo solid tumor growth of tested mice. The peptide compounds belong to the field of biomedicine. The functional micromolecular peptide compounds and the effect protein molecules of the functional micromolecular peptide compounds can inhibit in vitro human umbilical vein endothelial cells from forming vascular structures, inhibit vascularization in subcutaneous vaccination matrix gels of nude mice and inhibit growth of subcutaneous vaccination solid tumors of the nude mice. The invention not only provides a number of leading compounds capable of inhibiting neovascularization, but also discloses a new neovascularization regulating mechanism, thereby providing new target sites for developing a new generation of neovascularization inhibiting and antineoplastic drugs.

Description

technical field [0001] The invention relates to three polypeptide compounds based on the intracellular conserved sequence of the integrin β subunit and their effector molecules, which can effectively block the formation of new blood vessels in vivo and in vitro, and have the effect of inhibiting the growth of subcutaneous solid tumors in mice. Background technique [0002] Integrins are an important class of cell adhesion molecules located on the cell surface. They are transmodal heterodimeric glycoprotein receptors composed of α and β subunits linked by non-covalent bonds. Integrins are widely distributed in the human body, and almost all cells of different tissues express one or several integrin molecules. In vertebrates, 18 α and 8 β subunits have been found, and different combinations of α and β subunits form 24 α / β integrin heterodimers. Integrins are closely related to the occurrence and development of tumors. They participate in the formation of new blood vessels and...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/705A61K38/17A61P35/00
CPCA61K38/00C07K14/70557
Inventor 马衍青毛恺俊黄明来晶晶孙培森曹钟元褚羽丹锁昕凤许祯高娟
Owner SHANGHAI UNIV
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