AUTHOR=Wang Minghui , Gao Ruixuan , Sang Peng , Odom Timothy , Zheng Mengmeng , Shi Yan , Xu Hai , Cao Chuanhai , Cai Jianfeng TITLE=Dimeric γ-AApeptides With Potent and Selective Antibacterial Activity JOURNAL=Frontiers in Chemistry VOLUME=8 YEAR=2020 URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2020.00441 DOI=10.3389/fchem.2020.00441 ISSN=2296-2646 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 γ-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 γ-AApeptide derivatives as antibacterial agents.