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Dimeric γ-AApeptides With Potent and Selective Antibacterial Activity

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...

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Autores principales: Wang, Minghui, Gao, Ruixuan, Sang, Peng, Odom, Timothy, Zheng, Mengmeng, Shi, Yan, Xu, Hai, Cao, Chuanhai, Cai, Jianfeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304243/
https://www.ncbi.nlm.nih.gov/pubmed/32596202
http://dx.doi.org/10.3389/fchem.2020.00441
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author Wang, Minghui
Gao, Ruixuan
Sang, Peng
Odom, Timothy
Zheng, Mengmeng
Shi, Yan
Xu, Hai
Cao, Chuanhai
Cai, Jianfeng
author_facet Wang, Minghui
Gao, Ruixuan
Sang, Peng
Odom, Timothy
Zheng, Mengmeng
Shi, Yan
Xu, Hai
Cao, Chuanhai
Cai, Jianfeng
author_sort Wang, Minghui
collection PubMed
description 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.
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spelling pubmed-73042432020-06-26 Dimeric γ-AApeptides With Potent and Selective Antibacterial Activity Wang, Minghui Gao, Ruixuan Sang, Peng Odom, Timothy Zheng, Mengmeng Shi, Yan Xu, Hai Cao, Chuanhai Cai, Jianfeng Front Chem Chemistry 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. Frontiers Media S.A. 2020-06-12 /pmc/articles/PMC7304243/ /pubmed/32596202 http://dx.doi.org/10.3389/fchem.2020.00441 Text en Copyright © 2020 Wang, Gao, Sang, Odom, Zheng, Shi, Xu, Cao and Cai. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Chemistry
Wang, Minghui
Gao, Ruixuan
Sang, Peng
Odom, Timothy
Zheng, Mengmeng
Shi, Yan
Xu, Hai
Cao, Chuanhai
Cai, Jianfeng
Dimeric γ-AApeptides With Potent and Selective Antibacterial Activity
title Dimeric γ-AApeptides With Potent and Selective Antibacterial Activity
title_full Dimeric γ-AApeptides With Potent and Selective Antibacterial Activity
title_fullStr Dimeric γ-AApeptides With Potent and Selective Antibacterial Activity
title_full_unstemmed Dimeric γ-AApeptides With Potent and Selective Antibacterial Activity
title_short Dimeric γ-AApeptides With Potent and Selective Antibacterial Activity
title_sort dimeric γ-aapeptides with potent and selective antibacterial activity
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304243/
https://www.ncbi.nlm.nih.gov/pubmed/32596202
http://dx.doi.org/10.3389/fchem.2020.00441
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