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A kind of polypeptide targeting c-met and its application

A targeted, gln-ile-ile-ala-asn technology, applied to medical preparations containing active ingredients, peptides, peptide/protein components, etc., to achieve good proliferation, inhibit tumor growth in mice, and have no obvious adverse reactions and toxic side effects

Active Publication Date: 2022-06-07
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

A total of 48 drugs are under research, including 10 chemical drugs and 2 biological drugs under research. There is no peptide drug targeting this target, and there is no class 1 drug targeting this target in China.

Method used

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  • A kind of polypeptide targeting c-met and its application
  • A kind of polypeptide targeting c-met and its application
  • A kind of polypeptide targeting c-met and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] The polypeptides involved in this example were all obtained by solid-phase synthesis, and then the purity was detected by high performance liquid phase HPLC.

[0032] Each polypeptide sequence is as follows: Asp-Gln-Ile-Ile-Ala-Asn-Asn (CM 7-1), Ala-Gln-Ile-Ile-Ala-Asn-Asn (CM 7-2), Asp-Gln-Ile -Ile-Ala-Asn-Ala (CM 7-3), Asp-Gln-Ile-Ile-Ala-Asn (CM 7-4) or Gln-Ile-Ile-Ala-Asn (CM 7-5), pure All are above 95%. For test results see figure 1 . figure 1 A, the purity of CM 7-1 is 97.41%; figure 1 B, the purity of CM 7-2 is 97.84%; figure 1 The purity of C, CM 7-3 is 97.02%; figure 1 D, the purity of CM 7-4 is 95.31; figure 1 E, CM 7-5 was 95.43% pure.

Embodiment 2

[0034] The targeted c-Met polypeptides involved in the experiment were all combined by computer simulation through bioinformatics. In this experiment, one of the targeting c-Met polypeptides was specifically bound to the target protein at the cellular level to detect.

[0035] The present invention relates to a polypeptide with preventive and / or tumor-inhibiting activity, which has the amino acid sequence of the present invention. The polypeptide of the present invention has the amino acid sequence Xa-Gln-Ile-Ile-Ala-Asn-Xb, or a pharmaceutically acceptable salt thereof, wherein The Xa and Xb are any amino acid deletion or substitution.

[0036] In this example, the CM 7-1 polypeptide was mainly used as the object to study the polypeptides with anti-tumor and / or anti-tumor activities.

[0037] The main target of an active polypeptide with the ability to prevent and / or treat tumors involved in the present invention is c-Met. In this study, the designed c-Met-targeting polypepti...

Embodiment 3

[0046] MTT assay was used to detect the series of targeted c-MET series polypeptides inhibiting tumor cell proliferation.

[0047] 3.1 Experimental materials

[0048] Breast cancer cells MDA-MB-231, colon cancer cells HCT-116, pancreatic cancer cells PANC-1, ovarian cancer SKO V-3, liver cancer HepG-2, gastric cancer cells MKN-45, lung cancer cells A549, kidney cancer cells Caki- 1. Brain glioma cells U 87 and melanoma cells ME, DMEM medium, RPMI 1640 medium, McCoy's 5A medium, penicillin, streptomycin and fetal bovine serum (FBS), MTT.

[0049] 3.2 Experimental instruments

[0050] CO 2 Cell incubator, single-channel pipette, inverted microscope, liquid nitrogen tank, small centrifuge, ultra-clean bench, automatic high pressure steam sterilizer, oven, electronic balance, cell counter, 96-well plate.

[0051] 3.3 Experimental method

[0052] The above-mentioned tumor cell concentrations were adjusted to 2 × 10 4 cells / mL, spread evenly in 96-well plates, 100 μL / well. Aft...

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Abstract

The invention discloses an anti-tumor active polypeptide targeting c-Met and its use in tumors, belongs to the field of drugs for treating tumors, and specifically relates to a polypeptide dosage form targeting c-Met and its application in anti-tumor. The polypeptide of the present invention has an amino acid sequence Xa-Gln-Ile-Ile-Ala-Asn-Xb, or a pharmaceutically acceptable salt thereof, wherein Xa and Xb are any amino acid deletion or substitution. After a large number of experiments, it is known that the c-Met targeting peptide has a clear target. In vivo and in vitro experiments show that the sequence peptide can effectively inhibit the pathogenesis of c-Met-mediated cancers, including but not limited to breast cancer, colon cancer, pancreatic cancer, ovarian cancer , liver, stomach, lung, kidney, glioma or melanoma. The c-Met-targeted polypeptide designed by the present invention is scientific, reasonable, feasible and effective, and can be used as a therapeutic drug for the treatment of human tumors, which greatly expands the therapeutic spectrum of c-Met target drugs and provides new opportunities for future drug development. Ideas and prospects have significant social and market value.

Description

technical field [0001] The invention belongs to the field of biological medicine, and more particularly, relates to a polypeptide with antitumor activity and its application. Background technique [0002] With the deepening of scientific research, the treatment of malignant tumors has entered the era of individualization and precise targeting, and the development of new targets for individualized treatment of tumor patients has become a top priority. Hepatocyte growth factor receptor (c-Met) is a receptor tyrosine protein kinase encoded by the proto-oncogene MET, and hepatocyte growth factor (HGF) is the only known natural ligand for c-Met. A large number of clinical and basic studies have shown that the HGF / c-Met signaling pathway plays a crucial role in the occurrence and development of tumors, and has attracted much attention in the field of anti-tumor therapy in recent years. [0003] At present, Met receptor activation mechanisms mainly have the following four forms: (...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K7/06A61K38/08A61P35/00
CPCC07K7/06A61P35/00A61K38/00
Inventor 徐寒梅夏春磊刘晨
Owner CHINA PHARM UNIV
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