Gramicidin-S-Inspired Cyclopeptidomimetics as Potent Membrane-Active Bactericidal Agents with Therapeutic Potential

被引：3
|
作者：
Hu, Chengfei [1 ]
Wen, Quan [1 ]
Huang, Shuhui [2 ]
Xie, Saisai [1 ]
Fang, Yuanying [1 ]
Jin, Yi [1 ]
Campagne, Remy [3 ]
Alezra, Valerie [3 ]
Miclet, Emeric [4 ]
Zhu, Jinhua [5 ]
Wan, Yang [1 ,3 ]
机构：
[1] Jiangxi Univ Tradit Chinese Med, Natl Pharmaceut Engn Ctr Solid Preparat Chinese H, 1688 Meiling Ave, Nanchang 330004, Jiangxi, Peoples R China
[2] Jiangxi Maternal & Child Hosp, 318 Bayi Ave, Nanchang 330006, Jiangxi, Peoples R China
[3] Univ Paris Saclay, Univ Paris Sud, CNRS,Fac Sci Orsay, Lab Methodol Synth & Mol Therapeut ICMMO,UMR 8182, Bat 410, F-291405 Orsay, France
[4] PSL Univ, Sorbonne Univ, CNRS, Lab Biomol, 4 Pl Jussieu, F-75005 Paris, France
[5] Jiangxi Univ Tradit Chinese Med, Inst Tradit Chinese Med, 1688 Meiling Ave, Nanchang 330004, Jiangxi, Peoples R China
来源：
CHEMMEDCHEM | 2021年 / 16卷 / 02期
基金：
中国国家自然科学基金;
关键词：
peptidomimetics; antibiotics; membrane active; hemolysis; beta; gamma-diamino acids; ANTIMICROBIAL PEPTIDES; BETA; GAMMA-DIAMINO ACID; HEMOLYTIC-ACTIVITY; HYDROGEN-BOND; ANTIBIOTICS; ANTIBACTERIAL; SELECTIVITY;
D O I：
10.1002/cmdc.202000568
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Antimicrobial peptides (AMPs) are promising antibacterial agents often hindered by their undesired hemolytic activity. Inspired by gramicidin S (GS), a well-known cyclodecapeptide, we synthesized a panel of antibacterial cyclopeptidomimetics using beta,gamma-diamino acids (beta,gamma-DiAAs). We observed that peptidomimetic CP-2 displays a bactericidal activity similar to that of GS while possessing lower side-effects. Moreover, extensive studies revealed that CP-2 likely kills bacteria through membrane disruption. Altogether, CP-2 is a promising membrane-active antibiotic with therapeutic potential.
引用
收藏
页码：368 / 376
页数：9
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