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ANXA1 derived polypeptide and application thereof

A peptide and peptide sequence technology, applied in the field of anti-tumor ANXA1-derived peptides, can solve the problems of unreported biological significance of protein interaction, specificity and safety defects, etc.

Active Publication Date: 2019-12-13
XIANGYA HOSPITAL CENT SOUTH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although EphA2 inhibitors such as ALW-II-41-27 have entered clinical trials, their specificity and safety still have major defects
[0004] Both ANXA1 and EphA2 are potential tumor intervention targets, but the interaction between these two proteins and their biological significance have not been reported so far

Method used

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  • ANXA1 derived polypeptide and application thereof
  • ANXA1 derived polypeptide and application thereof
  • ANXA1 derived polypeptide and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0134] Example 1: Anti-nasopharyngeal carcinoma effect of N-terminal 20-30 amino acid polypeptide of ANXA1

[0135]The target peptide sequence used in the examples of the present invention is the amino acid sequence at the N-terminal 20-30 of ANXA1 connected to the commonly used membrane-penetrating peptide TAT sequence:

[0136] Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-Glu-Tyr-Val-Gln-Thr-Val-Lys-Ser-Ser-Lys-Gly, the single-letter sequence is YGRKKRRQRRR- EYVQTVKSSKG, with a purity of over 95% and good water solubility, was synthesized by Suzhou Qiangyao Biological Company.

[0137] Figure 8 A is the peptide design diagram. The amino acid sequence [A1(20-30)] of the N-terminal 20-30 of ANXA1 connected with TAT is the target peptide, the sequence is YGRKKRRQRRREYVQTVKSSKG, and the purity is over 96%. The sequence of the control peptide TAT is YGRKKRRQRRR, and the purity is above 96%. The designed peptide was synthesized by Suzhou Qiangyao Biological Company.

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Abstract

The invention provides an anti-tumor ANXA1 derived polypeptide and an application thereof. A series of experiment results prove that the ANXA1 is combined with the EphA2 to protect the EphA2 from being ubiquitinated and degraded by the E3 ubiquitin ligase Cbl, and 20-30 amino acids (namely EYVQTVKSSKG) and 28-30 amino acids (namely SKG) at the N end of the ANXA1 are key regions for combining the ANXA1 and the EphA2. In order to block the combination of ANXA1 and EphA2, 20-30 amino acid polypeptides at the N end of the ANXA1 are synthesized in vitro, the cell-penetrating peptide TAT is used forentering the tumor cells, so that the combination of the ANXA1 and the EphA2 in the tumor cells can be obviously blocked, the combination of Cbl and EphA2 is increased, the ubiquitination degradationof the EphA2 is promoted, the in-vitro and in-vivo growth of the tumor cells is inhibited, and a remarkable anti-tumor effect is achieved. Therefore, the EYVQTVKSSKG polypeptide can be used for preparing antitumor drugs, and has important clinical application value.

Description

technical field [0001] The invention belongs to the technical field of research and development and treatment of anti-tumor drugs, and in particular relates to an anti-tumor ANXA1-derived polypeptide and its application. Background technique [0002] Annexin belongs to the calcium-dependent phospholipid-binding protein superfamily, widely exists in mammals and humans, and is expressed in almost all organs. ANXA1 (Annexin 1) is the first identified member of this family, and it has many important physiological functions such as regulating inflammation, immunity, cell proliferation and apoptosis. Human ANXA1 protein is a cytoplasmic protein consisting of 346 amino acids and a molecular weight of 37kD, which is reversibly combined with the cell membrane depending on calcium ions. It is expressed in many epithelial tissues and inflammatory cells. Initial studies have shown that ANXA1 has anti-inflammatory and immune-modulating effects. Recent studies have found that ANXA1 is a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/47C07K19/00A61K38/17A61P35/00
CPCA61K38/00A61P35/00C07K14/4721C07K2319/10
Inventor 肖志强冯娟卢珊珊黄伟易红肖塔
Owner XIANGYA HOSPITAL CENT SOUTH UNIV
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