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Oligopeptides as full-length New Delhi metallo-β-lactamase-1 (NDM-1) inhibitors

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单位: [1]Wuhan Univ, Renmin Hosp, Dept Pharm, Wuhan, Peoples R China [2]Wuhan Univ, State Key Lab Virol, Wuhan, Peoples R China [3]Wuhan Univ, Renmin Hosp, Dept Clin Lab, Wuhan, Peoples R China [4]Wuhan Univ, Renmin Hosp, Cent Lab, Wuhan, Peoples R China [5]Huazhong Univ Sci & Technol, Tongji Hosp, Dept Gastroenterol, Tongji Med Coll, Wuhan, Peoples R China
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'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 beta-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 mu M and 68 mu M and also displayed favorable synergistic effects of the inhibitors in combination with ertapenem against genetic engineering-host E. coli BL21 (DE3)/pET30aNDM-1 and a clinical isolate of P. aeruginosa with bla(NDM-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 pi-pi interaction, contributed to the inhibitory activities.

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出版当年[2016]版:
大类 | 3 区 生物
小类 | 3 区 综合性期刊
最新[2025]版:
大类 | 3 区 综合性期刊
小类 | 3 区 综合性期刊
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出版当年[2015]版:
Q1 MULTIDISCIPLINARY SCIENCES
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Q1 MULTIDISCIPLINARY SCIENCES

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第一作者单位: [1]Wuhan Univ, Renmin Hosp, Dept Pharm, Wuhan, Peoples R China [2]Wuhan Univ, State Key Lab Virol, Wuhan, Peoples R China
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