The Chemistry of Peptidyltransferase Center-Targeted Antibiotics: Enzymatic Resistance and Approaches to Countering Resistance
The Chemistry of Peptidyltransferase Center-Targeted Antibiotics: Enzymatic Resistance and Approaches to Countering Resistance
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DOI：
10.1021/cb200418f
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发表时间：
2012-01-01
影响因子：
4
通讯作者：
Fujimori, Danica Galonic
中科院分区：
文献类型：
--
作者：
McCusker, Kevin P.;Fujimori, Danica Galonic
持续治疗细菌感染的能力需要有效的抗生素。新疗法的开发是由这些抗生素的作用机制和耐药性的知识指导的。在分子水平上理解和对抗抗生素耐药性机制的持续努力，除了提供对抗生素影响的潜在生化功能的深入了解外，还有可能指导新治疗策略的开发。抗生素与细菌核糖体内的肽基转移酶中心和相邻出口通道的相互作用是抗生素阻碍翻译从而停滞生长的主要机制。耐药酶催化组成这些功能区域的RNA的化学修饰，导致抗生素结合减少。本文综述了近年来在阐明耐药性的化学机制和推动新抗生素开发方面的进展。
The continued ability to treat bacterial infections requires effective antibiotics. The development of new therapeutics is guided by knowledge of the mechanisms of action of and resistance to these antibiotics. Continued efforts to understand and counteract antibiotic resistance mechanisms at a molecular level have the potential to direct development of new therapeutic strategies in addition to providing insight into the underlying biochemical functions impacted by antibiotics. The interaction of antibiotics with the peptidyltransferase center and adjacent exit tunnel within the bacterial ribosome is the predominant mechanism by which antibiotics impede translation, thus stalling growth. Resistance enzymes catalyze the chemical modification of the RNA that composes these functional regions, leading to diminished binding of antibiotics. This review discusses recent advances in the elucidation of chemical mechanisms underlying resistance and driving the development of new antibiotics.