Group of antimicrobial peptides and preparation method thereof

A monochloroacetyl sequence technology, applied in the field of medicine, can solve problems such as toxicity and short half-life

Active Publication Date: 2017-11-10
SHANGHAI INST OF PHARMA IND +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, natural cationic antimicrobial peptides are not perfect. Some antimicrobial peptides have certain toxicity to eukaryotes, and their high killing activity on pathogens is often accompanied by hemolysis to eukaryotes. Moreover, linear antimicrobial peptides are easily destroyed in the body. Hydrolyzed by various proteases, short half-life

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  • Group of antimicrobial peptides and preparation method thereof
  • Group of antimicrobial peptides and preparation method thereof
  • Group of antimicrobial peptides and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0058] Embodiment 1: Preparation and purification of TAMP-1

[0059] Amino acid sequence: iF-Lys-Arg-Leu-Lys-Lys-Leu-Leu-Lys-Lys-iF-NH 2 (SEQ ID NO:1)

[0060] (1) Materials and reagents

[0061] Rink Amide MBHA resin, substitution value 0.63mmol / g.

[0062] The amino acids are: Fmoc-L-Arg(Pbf)-OH, Fmoc-L-Leu-OH, Fmoc-L-Lys(Boc)-OH, Fmoc-L-4-iodophenylalanine-OH.

[0063] Reagents: HOBt, DIC, DMF, piperidine.

[0064] (2) Instrument

[0065] PSI300 peptide synthesizer, Waters600 semi-preparative high performance liquid chromatography, rotary evaporator, freeze dryer.

[0066] (3) Operation steps (take 0.15mmol as an example)

[0067] a. Solid-phase chemical synthesis of peptides

[0068] Weigh 0.24g of Rink Amide MBHA resin, place it in a polypeptide synthesizer reactor, add 15mL DMF, soak for 2h, then add 10mL of 20% PIP / DMF solution, mix for 30min to remove the amino protecting group, wash the resin 7 times with DMF, and then In reactor, add 0.45mmolFmoc-L-4-iodophen...

Embodiment 2

[0094] Example 2: Preparation and purification of cyclic peptide TAMP-14

[0095] Amino acid sequence: Loop (Caa-Phe-Lys-Lys-Leu-Leu-Lys-Lys-Leu-Arg-Lys-Cys) (SEQ ID NO: 14)

[0096] (1) Materials and reagents

[0097] Rink Amide MBHA resin, substitution value 0.63mmol / g.

[0098] The amino acids are: Fmoc-L-Cys(Trt)-OH, Fmoc-L-Lys(Boc)-OH, Fmoc-L-Arg(Pbf)-OH, Fmoc-L-Leu-OH, Fmoc-L-Phe- Oh.

[0099] Reagents: HOBt, DIC, DMF, piperidine, monochloroacetic acid.

[0100] (2) Instrument

[0101]PSI300 peptide synthesizer, Waters600 semi-preparative high performance liquid chromatography, rotary evaporator, freeze dryer.

[0102] Synthesize the sequence Rink Amide MBHA-Cys-Lys-Arg-Leu-Lys-Lys-Leu-Leu-Lys-Lys-Phe-Fmoc according to the operation step a in Example 1, then add 15 mL of 20% PIP / DMF solution, mix Remove the amino protecting group for 30 min, wash the resin 7 times with DMF, add 0.45 mmol of monochloroacetic acid, equimolar coupling reagent DIC (0.3 mol / L) and HOBt ...

Embodiment 3

[0103] Embodiment 3: Preparation and purification of the remaining TAMP series antimicrobial peptides in Table 5

[0104] (1) Materials and reagents

[0105] Rink Amide MBHA resin, substitution value 0.63mmol / g.

[0106] The amino acids are: Fmoc-L-Cys(Trt)-OH, Fmoc-L-Lys(Boc)-OH, Fmoc-D-Lys(Boc)-OH, Fmoc-L-Arg(Pbf)-OH, Fmoc-D -Arg(Pbf)-OH, Fmoc-L-Leu-OH, Fmoc-L-Ile-OH, Fmoc-D-Leu-OH, Fmoc-L-Phe-OH, Fmoc-D-Phe-OH, Fmoc- L-4-iodophenylalanine-OH, Fmoc-L-4,4-biphenylalanine-OH, Fmoc-L-4-trifluoromethylphenylalanine-OH, Fmoc-L-4 -Iodophenylalanine-OH, Fmoc-L-4-bromophenylalanine-OH, Fmoc-L-2,3,4,5,6-pentafluorophenylalanine.

[0107] Reagents: HOBt, DIC, DMF, piperidine, monochloroacetic acid.

[0108] (2) Instrument

[0109] PSI300 peptide synthesizer, Waters600 semi-preparative high performance liquid chromatography, rotary evaporator, freeze dryer.

[0110] (3) Operation steps (take 0.15mmol as an example)

[0111] Prepare and purify the polypeptides in Table 5 by a met...

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Abstract

The invention belongs to the field of medicine, and relates to a group of antimicrobial peptides and a preparation method thereof, particularly a group of cationic antimicrobial peptides, peptide derivatives and cyclic peptides with broad-spectrum antimicrobial activities, and a preparation method and applications thereof. The antimicrobial peptides have obvious bactericidal effects on Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, Candida albicans, drug-resistant Acinetobacter baumannii and drug-resistant Pseudomonas aeruginosa, and have the characteristics of broad spectrum and high efficiency.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to a group of cationic antibacterial peptides, peptide derivatives, cyclic peptides and their preparation methods and applications with broad-spectrum antibacterial activity. Background technique [0002] Since the discovery of penicillin, antibiotics have been a powerful weapon for humans to treat pathogenic microbial infections. However, with the abuse of traditional antibiotics, more and more pathogenic bacteria have begun to develop resistance to traditional antibiotics. Therefore, it is urgent to find a new class of antibacterial drugs. Use instead of antibiotics. [0003] Natural antimicrobial peptides are small molecular polypeptides produced by gene coding or hydrolysis of macromolecular proteins, generally cationic (rich in lysine and arginine) polypeptides composed of 12-50 amino acid residues, and are the host's defense against foreign microorganisms. One of the defen...

Claims

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Application Information

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IPC IPC(8): C07K7/06C07K7/64C07K1/04C07K1/06C07K1/18C07K1/20A61K38/08A61K38/12A61P31/04A61P31/10
CPCC07K7/06C07K7/64A61K38/00Y02P20/55Y02A50/30
Inventor 冯军张喜全唐汉卿东圆珍李亚茹徐一帆
Owner SHANGHAI INST OF PHARMA IND
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