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Dimeric ?-AApeptides With Potent and Selective Antibacterial Activity.

ABSTRACT: Over the past few decades, the emergence of antibiotic resistance developed by life-threatening bacteria has become increasingly prevalent. Thus, there is an urgent demand to develop novel antibiotics capable of mitigating this trend. Herein, we report a series of dimeric ?-AApeptide derivatives as potential antibiotic agents with limited toxicity and excellent selectivity against Gram-positive strains. Among them, compound 2 was identified to have the best MICs without inducing drug resistance, even after exposure to MRSA for 20 passages. Time-kill kinetics and mechanistic studies suggested that 2 could mimic host-defense peptides (HDPs) and rapidly eradicate MRSA within 2 hours through disturbing the bacteria membrane. Meanwhile, biofilm formation was successfully inhibited even at a low concentration. Taken together, these results suggested the great potential of dimeric ?-AApeptide derivatives as antibacterial agents.

SUBMITTER: Wang M

PROVIDER: S-EPMC7304243 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Dimeric γ-AApeptides With Potent and Selective Antibacterial Activity.

Wang Minghui M Gao Ruixuan R Sang Peng P Odom Timothy T Zheng Mengmeng M Shi Yan Y Xu Hai H Cao Chuanhai C Cai Jianfeng J

Frontiers in chemistry 20200612

Over the past few decades, the emergence of antibiotic resistance developed by life-threatening bacteria has become increasingly prevalent. Thus, there is an urgent demand to develop novel antibiotics capable of mitigating this trend. Herein, we report a series of dimeric γ-AApeptide derivatives as potential antibiotic agents with limited toxicity and excellent selectivity against Gram-positive strains. Among them, compound <b>2</b> was identified to have the best MICs without inducing drug resi ...[more]

PMID: 32596202

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