Polyglycol modified antimicrobial peptide and uses thereof

A polyethylene glycol and antibacterial peptide technology, applied in the field of modification of peptides, can solve the problems such as the reduction of antibacterial activity of antibacterial peptides

Inactive Publication Date: 2009-05-13
NANKAI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] According to the above-mentioned antimicrobial peptides are easily degraded by proteases in vivo, the molecular weight of PEG has contradictory effects on the anti-proteolytic enzyme effect and drug efficacy of modified polypeptide drugs, and PEG modification often makes the antibacterial activity of antimicrobial peptides significantly reduced. problem, presenting the invention of the present invention

Method used

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  • Polyglycol modified antimicrobial peptide and uses thereof
  • Polyglycol modified antimicrobial peptide and uses thereof
  • Polyglycol modified antimicrobial peptide and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0013] Synthesis of polypeptide MA resin with side chain protecting groups: add 1g Rinkamide MBHA resin (0.74mmol / g) to a 50mL reaction bottle, add 15mL dimethylformamide (DMF) to swell for 10 minutes, remove the solvent by suction filtration, then add 15mL 20% piperidine / DMF solution, stirred for 30 minutes, and suction filtered. The resin was washed 6 times with DMF, and the solvent was removed by suction filtration. Add 1.44g Fmoc-Arg(Pbf)-OH (Pbf is 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl), 0.46g (2.22mmol) DIC to the reaction flask (N,N-Diisopropylcarbodiimide) and 0.30g (2.22mmol) HOBt (1-hydroxybenzotriazole) and 15mL DMF were stirred at room temperature to react. After 2 hours of reaction, a small amount of resin was taken for ninhydrin color test, and the result showed that the condensation reaction was complete. Suction filtration, wash the resin 6 times with DMF, and remove the solvent by suction filtration. The first (protected) amino acid at the C-ter...

Embodiment 2

[0015] The preparation of polypeptide MA: the polypeptide MA resin 0.5g that embodiment 1 obtains is joined in the 50mL round-bottomed flask, adds 10mLK reagent (trifluoroacetic acid / water / phenol / sulfide anisole / 1,2-dimercaptoethylene glycol =82.5 / 5 / 5 / 5 / 2.5, volume ratio), stirred at room temperature for 4 hours. Filter and collect the filtrate. The resin was washed three times with trifluoroacetic acid. The filtrates were combined, and most of the trifluoroacetic acid was removed by rotary evaporating the filtrate, and 8-10 times the volume of ether was added to precipitate the polypeptide MA, and the ether precipitate was placed in the refrigerator overnight. Centrifuge to remove ether, and dry in vacuo to obtain crude polypeptide MA.

[0016]Dissolve 200mg of polypeptide MA crude product in 5mL of pure water, and purify by preparative reverse-phase HPLC. , volume ratio), the flow rate is 12mL / min. The collected solution was concentrated by rotary evaporation, and then f...

Embodiment 3

[0018] Polyethylene glycol carboxyl derivatives (mPEG 500 -COOH) Preparation: Mix 3.2g of mPEG-OH with an average molecular weight of 500, 20g of distilled water and 0.4g of KOH, cool to 0.5°C with an ice-salt bath, and slowly add 0.4g of acrylonitrile dropwise. The solution was stirred at 0-5°C for 2 hours. Slowly add 30g of concentrated sulfuric acid dropwise, and heat at 95-100°C for 3 hours. After cooling to room temperature, add 200 mL of distilled water and extract with dichloromethane 3 times, 30 mL each time. Dichloromethane extract with anhydrous Na 2 SO 4 After drying, the solvent was evaporated under reduced pressure to obtain mPEG 500 -COOH.

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Abstract

The invention relates to a series of polyethylene glycol modified cationic antibacterial peptide with different molecular weight. The modified antibacterial peptide is self-assembled into a nanometer micelle in an aqueous medium. The formation of the micelle can play a role in protecting the antibacterial peptide and weakening the degradation effect of protease on the antibacterial peptide, and simultaneously improves the stability and antibacterial activity of polypeptide in serum. In addition, the modification of polyethylene glycol obviously reduces the hemolytic toxic side effects of the antibacterial peptide.

Description

technical field [0001] The present invention relates to the modification of polypeptides, specifically polyethylene glycol-modified cationic antimicrobial peptides. The polyethylene glycol-modified cationic antimicrobial peptides are self-assembled in aqueous media to form antimicrobial peptides as cores and polyethylene glycol as shells. bundle, thereby reducing the degradation of antimicrobial peptides by proteases. Background technique [0002] In recent years, cationic antimicrobial peptides and their analogues have attracted great attention as a new generation of antibiotics against drug-resistant bacteria. Especially with the widespread use of traditional antibiotics, bacteria have gradually developed resistance to them, forcing people to constantly search for new antibiotics, cationic antimicrobial peptides are not easy to develop resistance to them due to the unique antibacterial mechanism of bacteria (M .Zasloff, Nature, 2002, 415, 389-395) and has received extensi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/08C07K1/107C07K1/04C07K1/06
CPCY02P20/55
Inventor 阎虎生张更辉林小燕韩宝中
Owner NANKAI UNIV
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