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

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Problems solved by technology

However, antimicrobial peptides can not only act on microbial cell membranes, but also lyse

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
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Example Embodiment

[0114] Example 1. Reconstruction method of antimicrobial peptides and preparation of antimicrobial peptide derivatives

[0115] 1. Reconstruction method of antimicrobial peptides

[0116] The antimicrobial peptide modification method of the present invention is to replace any amino acid residue except lysine Lys and arginine Arg with lysine Lys in the antimicrobial peptide. Antibacterial peptides with a single amino acid residue replaced are denoted as antibacterial 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 Table 1. Gil...

Example Embodiment

[0128] Example 2. Application of antimicrobial peptide derivatives

[0129] 1. Application of GF-17 antimicrobial peptide derivatives

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

[0131] Antibacterial peptide derivatives tested: GF-17 antibacterial peptide derivatives aGF1-aGF12 prepared in Example 1, and GF-17 antibacterial peptide was used as a control.

[0132] The hemolytic ability (the ability to dissolve erythrocytes) of GF-17 antimicrobial peptide and GF-17 antimicrobial peptide derivatives was measured according to the following method, respectively. Specific steps are as follows:

[0133] 1) Fresh human 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) washed three times, centrifuged at 450 × g for 5 min each time, then the compacted red blood cells were made into a 1.25% red blood cell suspension with PBS buffer, and 160 μl of the red blood cell suspension wa...

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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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