Oligopeptide derivative capable of combination of basic fibroblast growth factor, and application thereof

A technology of fibroblasts and growth factors, which can be applied in the fields of peptides, drug combinations, anti-tumor drugs, etc., and can solve problems such as reports of peptide derivatives antagonists that have not yet been found.

Inactive Publication Date: 2012-04-04
WENZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are very few reports on peptide antagonists of bFGF, and no reports of peptide derivative antagonists have been found

Method used

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  • Oligopeptide derivative capable of combination of basic fibroblast growth factor, and application thereof
  • Oligopeptide derivative capable of combination of basic fibroblast growth factor, and application thereof
  • Oligopeptide derivative capable of combination of basic fibroblast growth factor, and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] peptide synthesis

[0028] By the solid-phase peptide synthesis method, a 413A automatic peptide synthesizer (purchased from Perkin Elmer) was used to synthesize the peptide shown in the following sequence: N'-Pro-Ile-Leu-Gln-Ala-Gly-Leu-Gly- Gly-Gly-Ser-NH2-C', wherein the amino acid residues are all L-type amino acids. The specific process of synthesis is as follows: Rink Amide-AM Resin resin is used as the carrier; Fmoc is used as the protecting group of the amino acid α-amino group; DMF is used as the reaction solvent; the activator is HBTu: 0.5M (DMF) and NMM (N-methylmorpholine ), 2M (DMF); DMF containing 20% ​​piperidine was used as the deprotecting agent; the lysate was 95% TFA and 5% (H2O+EDT+Tis). Peptides were precipitated with anhydrous ether. Precipitation in water / tert-butanol (1:1) and lyophilization afforded the crude peptide. The crude peptide was purified by reverse phase HPLC in 30 minutes with a gradient of 37-42% acetonitrile / 0.9% TFA. It was th...

Embodiment 2

[0030] Inhibitory activity of P21 on the proliferation of NIH3T3 cells induced by bFGF

[0031] Select NIH3T3 cells expressing more bFGF receptors, inoculate 6000 cells / well in 96-well culture plate, 100 μl per well, 10% FBS (imported) DMEM low-glucose medium; after overnight, replace with 0.1% FBS The DMEM low-glucose medium was cultured for 24 hours; the mixture of bFGF and P21 was added, the final concentration of bFGF was 20 ng / ml, and the final concentrations of peptides were 0.25, 1.00, 4.00, and 16.00 μM, respectively. After 48 hours, the OD value at 490nm was measured by MTT method, and the inhibition rate was calculated. The test includes: blank group, no bFGF and peptide; negative group, only bFGF (20ng / mL) and no peptide; drug-dosed test group; blank group and negative group are added with the same volume of PBS as the drug-dosed test group . The calculation formula of inhibition rate=[OD (negative group)-OD (test group)] / [OD (negative group)-OD (blank group)]*100...

Embodiment 3

[0033] Inhibitory activity of P21 on bFGF-induced cell proliferation

[0034] Select Balb / c 3T3, lung cancer (A549) cells, and glioma (U251) cells expressing more bFGF receptors, and inoculate 6000 cells / well in 96-well culture plates, 100 μl per well, medium Use DMEM high-glucose medium with 10% FBS; after overnight, replace with 0.1% FBS medium for 24 hours; add the mixture of bFGF and P21, the final concentration of bFGF is 20ng / ml, and the final concentration of peptide is 4.00μM . After 48 hours, the OD value at 490nm was measured by MTT method, and the inhibition rate was calculated. The test includes: blank group, no bFGF and peptide; negative group, only bFGF (20ng / mL) and no peptide; drug-dosed test group; blank group and negative group are added with the same volume of PBS as the drug-dosed test group . The calculation formula of inhibition rate=[OD (negative group)-OD (test group)] / [OD (negative group)-OD (blank group)]*100%. For inhibitory activity data on cell...

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Abstract

The invention belongs to the technical fields of medicinal chemistry and polypeptide biology, and relates to an oligopeptide derivative P15 capable of combination of basic fibroblast growth factor (bFGF), wherein the sequence of the P15 is N'-PILQAGLGGGS-NH2-C'. The invention specifically relates to the sequence of the P15, and an application of the P15 in fields of basic research and medicine. The present invention further comprises various peptide derivatives of the P15, wherein the P21 is the peptide derivative of the P15, and the sequence of the P21 is N'-PLLQA TA GGGS-NH2-C'. With combination of the bFGF, the P15 and the P21 can provide good inhibition activities for bFGF-induced NIH3T3 cell proliferation and bFGF-induced Bable / C 3T3 cell proliferation, can significantly inhibit proliferations of bFGF-induced lung cancer A549 cells and bFGF-induced glioma U251 cells, and provide prospects for development into anti-tumor peptide drugs.

Description

Technical field: [0001] The invention belongs to the fields of medicinal chemistry and polypeptide biotechnology, and relates to a short peptide derivative capable of binding to basic fibroblast growth factor, specifically to its sequence, and its application in the fields of basic research and medicine. Background technique: [0002] Basic fibroblast growth factor (bFGF, or FGF2) binds and activates the corresponding receptor (FGFR), which plays an important role in mitogenic and non-mitogenic biological functions. However, it has been found that colon cancer, prostate cancer, fibroma, rhabdomyosarcoma, glioma, melanoma and other tumors are closely related to the abnormal up-regulation of bFGF expression. Therefore, bFGF has attracted much attention as one of the therapeutic targets for diseases such as tumors. Antagonist drugs targeting bFGF can block the signal transmission of bFGF, inhibit the formation of new blood vessels in tumor tissue, and inhibit the growth, divis...

Claims

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Application Information

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IPC IPC(8): C07K7/06A61K38/08A61P35/00
Inventor 吴建章李校堃吴晓萍梁广叶辉蔡跃飘陈玲姿
Owner WENZHOU MEDICAL UNIV
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