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A ph-responsive non-helix-helix transition antimicrobial polypeptide and preparation method thereof

A non-helix and helical technology, applied in the field of non-helix-helix transformation antibacterial polypeptide materials and their preparation, can solve the problems of difficult to achieve precise control, low pH response sensitivity, complex synthesis process, etc., to reduce toxicity and improve antibacterial effect. , the effect of reducing hemolytic activity

Active Publication Date: 2021-08-06
SOUTH CHINA UNIV OF TECH +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Early studies mostly revolved around polyglutamic acid and polylysine. However, the controllability of polyglutamic acid and polylysine is poor, and only under extremely acidic or alkaline conditions will there be secondary structures. transformation, it is difficult to apply under physiological conditions
Xiong Menghua and others applied polyglutamic acid copolymers to kill Helicobacter pylori in the stomach, and realized the transition from non-helical to helical under gastric acid conditions to achieve the killing of bacteria, but the synthesis process is very complicated and the pH response sensitivity is low. Difficult to achieve precise control

Method used

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  • A ph-responsive non-helix-helix transition antimicrobial polypeptide and preparation method thereof
  • A ph-responsive non-helix-helix transition antimicrobial polypeptide and preparation method thereof
  • A ph-responsive non-helix-helix transition antimicrobial polypeptide and preparation method thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0074] A pH-responsive non-helix-helix transition antimicrobial polypeptide route such as figure 1 , the specific method is as follows:

[0075] 1) Preparation of glutamic acid derivative ButLG

[0076] Take 10g of glutamic acid in a 250mL round-bottomed flask, add 15mL of anhydrous 3-buten-1-ol, place the round-bottomed flask in an ice-water bath, add 4mL of concentrated sulfuric acid under stirring conditions, remove the ice-water bath, and stir React for 12 hours until the reaction solution becomes colorless and transparent; adjust the pH of the reaction solution to 7.0 with saturated sodium carbonate, remove the liquid by suction filtration, wash twice with deionized water to remove inorganic salts; transfer the white solid to a 250 mL circular Add 4mL isopropanol and 4mL deionized water to the bottom flask, heat to 80°C with an oil bath and stir until completely dissolved and become colorless and transparent. Stop stirring and cool down to room temperature; remove the li...

Embodiment 2

[0092] Secondary Structure Regulation of a pH-Responsive Non-Helix-Helix Transition Antimicrobial Polypeptide

[0093] 1) The charge of the side chain of the polypeptide affects the helical structure of the polypeptide

[0094] By introducing different numbers of maleic anhydride modifications into the side chain of the polypeptide PButLG-CA, circular dichroism was measured to explore the influence of the number of negative charges introduced by the side chain on the secondary structure of the polypeptide, such as Figure 7 X in Part A of X represents the amount of maleic anhydride modified by the side chain, and the helical structure is the weakest when the side chain is modified with 5 maleic anhydrides. Figure 7 It is more intuitively reflected by the calculation of helicity in part B of , when the side chain introduces half of the heterogeneous charge, the helicity is the lowest.

[0095] 2) Synthesis of unresponsive non-helical polypeptide PButLG-MA

[0096] Weigh 1.0g...

Embodiment 3

[0101] Antibacterial activity and hemolytic toxicity of pH-responsive non-helical-helical transition antimicrobial peptides

[0102] 1) Hemolysis test:

[0103] Take an appropriate amount of sheep whole blood in a centrifuge tube, dilute it with 1×PBS, and prepare a 4% (v / v) sheep blood solution; use PBS to prepare a series of drug solutions, add 100 μL / tube to the EP tube, and then add Equal volume of 4% sheep blood; PBS and equal volume of 4% sheep blood were mixed as a negative control group; 0.1% Triton and equal volume of 4% sheep blood were mixed as a positive control group; samples were mixed and placed in Incubate at 37°C for 60min. Subsequently, the sample was placed at 4°C for centrifugation (1000rpm / 5min); after centrifugation, 100 μL of the supernatant was taken into a 96-well plate, and the absorbance was measured at 576nm to calculate the hemolysis rate. The calculation formula is as follows: hemolysis=(OD 实验组 -OD 阴性组 )÷(OD 阳性组 -OD 阴性组 )×100%. Such as Fi...

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Abstract

The invention discloses a pH-responsive non-helix-helix transition antibacterial polypeptide and a preparation method thereof. The method uses glutamic acid, an essential amino acid with biocompatibility, as a raw material, combined with the click chemistry method, to obtain a cationic polypeptide with a helical structure, which is prepared by modifying half of the maleic anhydride derivative through the side chain of the cationic polypeptide with a helical structure. The pH-responsive non-helical-helical transition antibacterial polypeptide has simple process, convenient operation and low cost, and can efficiently realize the secondary structure transformation under specific pH conditions, effectively reduce the biotoxicity of cationic polypeptides, and improve the bioavailability of cationic polypeptides Spend. In the present invention, through the modification of acid anhydrides with different pH responses, non-helical-helical transition antibacterial polypeptides with different pH conditions can be obtained, and the transformation from a low-activity non-helical structure to a high-activity helical structure can be realized under different physiological conditions. The conversion of cationic peptides can kill bacteria at the site of infection, which has broad application prospects.

Description

technical field [0001] The invention belongs to the field of polypeptide materials, and in particular relates to a pH-responsive non-helix-helix transition antibacterial polypeptide material and a preparation method thereof. Background technique [0002] More than 7,000 naturally occurring peptides have been identified that often play important roles in human physiology, including hormones, neurotransmitters, growth factors, ion channel ligands, or anti-infective drugs. Over the past decade, peptides have been widely used in medicine and biotechnology, and research on therapeutic peptides is experiencing a renaissance for commercial reasons. Compared with natural polypeptides, polymeric synthetic polypeptides are mostly macromolecules with simple sequences, in which amino acids are repeated many times, and retain the tendency to adopt ordered secondary conformations, such as α-helices or β-sheets, which are common in other polymers. rare. In fact, due to the degradability ...

Claims

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Application Information

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IPC IPC(8): C07K7/06C07K7/08C07K1/02C08G69/48C08G69/00A61P31/04
CPCA61P31/04C07K7/06C07K7/08C08G69/00C08G69/48
Inventor 熊梦华李杰袁月玲鲍燕章欣爽黄芮
Owner SOUTH CHINA UNIV OF TECH
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