PH (Potential of Hydrogen) response antibacterial peptide as well as preparation method and application thereof

A technology of antimicrobial peptides and amino acids, applied in the field of pH-responsive antimicrobial peptides and their preparation, can solve the problems of reduced antibacterial effect, achieve the effects of reduced toxicity, high selectivity, and improved biocompatibility

Active Publication Date: 2019-01-18
TECHNICAL INST OF PHYSICS & CHEMISTRY - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For example, grafting polyethylene glycol (PEG) to the N-terminus of the antimicrobial peptide CaLL can improve the compatibility of the antimicrobial peptide with lung tissue, but at the same time the antibacterial effect is reduced by 50% (Morris, C.J.Antimicrob.Agents Chemother. 2012,56,3298-3308.); Grafting cationic polypeptide KSLW onto PEG-modified phospholipid micelles can also improve cytocompatibility while maintaining antibacterial activity (Lee, W. Theranostics2017, 7, 3759-3767. ), design and synthesize artificial antimicrobial peptides and their derivatives to reduce cytotoxicity and maintain antibacterial activity (G.N.Tew Acc.Chem.Res.2010,43,30.)

Method used

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  • PH (Potential of Hydrogen) response antibacterial peptide as well as preparation method and application thereof
  • PH (Potential of Hydrogen) response antibacterial peptide as well as preparation method and application thereof
  • PH (Potential of Hydrogen) response antibacterial peptide as well as preparation method and application thereof

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preparation example Construction

[0036] In the prior art, although natural antibacterial peptides (melitin, bombesin, etc.) have good antibacterial effects, they also have very high cytotoxicity, low protease stability, and high production costs. These shortcomings limit natural antibacterial peptides. Applications. In order to solve the problems in the prior art, the present invention provides a pH-responsive antibacterial peptide and a preparation method and application thereof.

[0037] The first object of the present invention is to provide two antimicrobial peptides with similar structures and simple amino acid sequences.

[0038] The second object of the present invention is to provide a pH-responsive antibacterial peptide, which can not only maintain the bactericidal performance of the antibacterial peptide at the bacterial infection site, but also reduce its toxicity to mammalian cells.

[0039] The third object of the present invention is to provide a method for preparing antimicrobial peptides that modify...

Embodiment 1

[0064] The amino acid sequence of the antimicrobial peptide is LKLLKKLLKKLKKLLKKL (18 peptides), and the structural formula of the antimicrobial peptide is LKLLKKLLKKLKKLLKKL-NH 2 .

[0065] Note: The C-terminal contains -NH in the structural formula of antimicrobial peptide 2 Those skilled in the art can understand that the carboxyl amidation of antibacterial peptides is a conventional treatment method for antibacterial peptides.

[0066] The preparation method of the above antimicrobial peptide:

[0067] 1. Resin swelling

[0068] Put a certain amount of resin into the reaction tube, add DCM (dichloromethane), and shake for 30 minutes to swell the resin.

[0069] 2. Deprotection

[0070] The resin was washed three times with DMF (dimethylformamide), deprotected with the deprotection solution DBLK (a mixture of piperidine and DMF) for 15 minutes, and then washed with DMF six times.

[0071] 3. Connect the first amino acid

[0072] After filtering off the solvent, add 3-fold molar excess o...

Embodiment 2

[0081] The amino acid sequence of the antimicrobial peptide is KKLL (4 peptides), and the structural formula of the antimicrobial peptide is KKLL-NH 2 .

[0082] The preparation steps of the above antimicrobial peptides are basically the same as in Example 1, except that the sequence of coupling amino acids should be carried out according to the amino acid sequence of this example.

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Abstract

The invention discloses pH (Potential of Hydrogen) response antibacterial peptide as well as a preparation method and application thereof. The invention firstly provides the antibacterial peptide witha simple amino acid sequence and the amino acid sequence only comprises hydrophilic lysine and hydrophobic leucine, but has key factors with an antibacterial effect of natural antibacterial peptide:positive charge, a hydrophobic domain, amphipathy, alpha helix secondary conformation and the like; the end part of the antibacterial peptide is simply modified and the bioactivity of the antibacterial peptide can be maintained; and meanwhile, the biocompatibility is improved. According to the pH response antibacterial peptide provided by the invention, an acid response molecule is modified on anantibacterial polypeptide chain, and the polypeptide can have a sterilization effect in a slightly-acidic environment of a bacterial infection part and also has the effect of reducing the toxicity ofthe antibacterial peptide on mammalian cells in a physiological environment.

Description

Technical field [0001] The invention relates to the technical field of antibacterial peptides. More specifically, it relates to a pH-responsive antibacterial peptide and its preparation method and application. Background technique [0002] In recent years, more and more pathogenic bacteria have developed resistance to antibiotics, and there is an urgent need to develop new antibacterial agents. Antimicrobial peptides (AMPs) are peptides with antibacterial activity in organisms. The number of amino acids is usually 10-50, and they are often positively charged and have broad-spectrum antibacterial activity. AMPs are an important part of the innate non-specific defense system of most organisms against invading pathogens. They have a unique antibacterial action mechanism, quickly kill bacteria and are not easy to cause bacterial resistance. They can be used alone or in combination with antibiotics to kill pathogens. Traditional antibiotics usually target a single enzyme to control ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/00C07K1/34A61K38/16A61P31/04
CPCA61K38/00A61P31/04C07K14/00
Inventor 牛忠伟鞠晓燕
Owner TECHNICAL INST OF PHYSICS & CHEMISTRY - CHINESE ACAD OF SCI
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