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High-efficiency and low-toxicity antibacterial peptide derivative and application thereof in preparation of antibacterial infection drug

An antibacterial peptide, the technology in the sequence table, applied in the application field of high-efficiency and low-toxicity antibacterial peptide derivatives, the preparation of anti-bacterial infection drugs, can solve the problems of cytotoxicity, hindering clinical application and the like

Pending Publication Date: 2020-11-06
ACADEMY OF MILITARY MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, antimicrobial peptides can not only act on microbial cell membranes, but also lyse the cell membranes of eukaryotic cells, resulting in cytotoxicity, which hinders its clinical application

Method used

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  • High-efficiency and low-toxicity antibacterial peptide derivative and application thereof in preparation of antibacterial infection drug
  • High-efficiency and low-toxicity antibacterial peptide derivative and application thereof in preparation of antibacterial infection drug
  • High-efficiency and low-toxicity antibacterial peptide derivative and application thereof in preparation of antibacterial infection drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0114] Embodiment 1, the modification method of antimicrobial peptide and the preparation of antimicrobial peptide derivative

[0115] 1. Modification method of antimicrobial peptides

[0116] The antimicrobial peptide modification method of the present invention is to replace any amino acid residue in the antimicrobial peptide except lysine Lys and arginine Arg with lysine Lys. Antimicrobial peptides with single amino acid residues substituted are referred to as antimicrobial peptide derivatives.

[0117] 2. Preparation of Antimicrobial Peptide Derivatives

[0118] 1. Preparation of GF-17 antimicrobial peptide derivatives

[0119] Taking GF-17 antimicrobial peptide as an example, the GF-17 antimicrobial peptide was modified according to the modification method in step 1 to obtain a group of GF-17 antimicrobial peptide derivatives, named aGF1-aGF12. The amino acid sequences of GF-17 antimicrobial peptide and GF-17 antimicrobial peptide derivatives aGF1-aGF12 are shown in Ta...

Embodiment 2

[0128] Embodiment 2, the application of antimicrobial peptide derivative

[0129] 1. Application of GF-17 Antibacterial Peptide Derivatives

[0130] 1. Determination of hemolytic ability of GF-17 antimicrobial peptide derivatives

[0131] Antimicrobial peptide derivatives to be tested: GF-17 antimicrobial peptide derivatives aGF1-aGF12 prepared in Example 1, and GF-17 antimicrobial peptide as a control.

[0132] The hemolytic ability of the GF-17 antimicrobial peptide and the GF-17 antimicrobial peptide derivative (the ability to lyse erythrocytes) was determined according to the following method. Specific steps are as follows:

[0133] 1) Human fresh whole blood was washed with PBS buffer (135mM NaCl, 2.7mM KCl, 1.5mM KH 2 PO 4 , and 8mMK 2 HPO 4 , pH 7.2) and washed three times, and centrifuged at 450×g for 5 min each time, then the compacted erythrocytes were made into a 1.25% packed erythrocyte suspension with PBS buffer, and 160 μl of the erythrocyte suspension was ...

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Abstract

The invention discloses a high-efficiency and low-toxicity antibacterial peptide derivative and an application thereof in preparation of an antibacterial infection drugs. Any amino acid residue, except lysine Lys and arginine Arg, in the GF-17 antibacterial peptide and the SAAP-148 antibacterial peptide is replaced with lysine Lys, and two groups of novel antibacterial peptide derivatives which are low in cytotoxicity, high in treatment index and good in biocompatibility are obtained. Experiments prove that compared with natural antibacterial peptide, the novel antibacterial peptide derivativedisclosed by the invention has higher selective toxicity to bacteria, that is, the novel antibacterial peptide derivative has the same or stronger bactericidal effect as the natural antibacterial peptide, the cytotoxicity to human is obviously reduced, and the influence on red blood cells is extremely low. The novel antibacterial peptide derivative disclosed by the invention has a broad-spectrumkilling effect on gram-positive bacteria or gram-negative bacteria, can be used for treatment of diseases caused by infection of antibiotic-resistant gram-positive bacteria or gram-negative bacteria,and has a bright application prospect.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to high-efficiency and low-toxic antibacterial peptide derivatives and their application in the preparation of antibacterial infection drugs. Background technique [0002] The emergence of drug-resistant bacteria, especially multidrug-resistant bacteria, is increasingly threatening human health. Among them, multidrug-resistant bacteria "ESKAPE" (Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter) are the most threatening. Antimicrobial peptides (AMPs) are polypeptide substances whose mechanism of action is obviously different from that of traditional antibiotics and can quickly kill bacteria, fungi, viruses and parasites, and are expected to become new drugs for the treatment of infectious diseases. Unlike traditional antibiotics, it is generally believed that the target of antimicrobial peptides is the ...

Claims

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Application Information

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IPC IPC(8): C07K7/08C07K14/47A61K38/10A61K38/17A61P31/04
CPCC07K7/08C07K14/4723A61P31/04A61K38/00Y02A50/30
Inventor 张士坤宫锋檀英霞李素波张雪贠志敏高红伟
Owner ACADEMY OF MILITARY MEDICAL SCI
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