PLoS One | |
Oligopeptides as full-length New Delhi metallo-β-lactamase-1 (NDM-1) inhibitors | |
Gang Liu1  Xiang Gao2  Jinchun Song3  Bingzheng Shen3  Yan Yu3  Chengliang Zhu4  | |
[1] Central Laboratory, Renmin Hospital, Wuhan University, Wuhan, China;Department of Clinical Laboratory, Renmin Hospital, Wuhan University, Wuhan, China;Department of Pharmacy, Renmin Hospital, Wuhan University, Wuhan, China;State Key Laboratory of Virology, Wuhan University, Wuhan, China | |
关键词: Zinc; Antibiotics; Pseudomonas aeruginosa; Enzyme inhibitors; Genetic engineering; Antibacterials; Hydrogen bonding; Sulfur; | |
DOI : 10.1371/journal.pone.0177293 | |
学科分类:医学(综合) | |
来源: Public Library of Science | |
【 摘 要 】
‘Superbug’ bacteria producing NDM-1 enzyme causing wide public concern were first detected in a patient who visited India in 2008. It's an effective approach to combining β-lactam antibiotics with NDM-1 inhibitor for treating NDM-1 producing strain infection. In our research, we designed ten oligopeptides, tested IC50 values against NDM-1 enzyme, determined the MIC values of synergistic antibacterial effect and explored the binding model. We found that the oligopeptides 2 (Cys-Phe) and 5 (Cys-Asp) respectively presented IC50 values of 113 μM and 68 μM and also displayed favorable synergistic effects of the inhibitors in combination with ertapenem against genetic engineering-host E. coli BL21 (DE3)/pET30a-NDM-1 and a clinical isolate of P. aeruginosa with blaNDM-1. Flexible docking and partial charge study suggested the interaction between oligopeptide and NDM-1. Three types of action effects, hydrogen bond, electrostatic effect and π-π interaction, contributed to the inhibitory activities.
【 授权许可】
CC BY
【 预 览 】
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