Kim S, Lee S W, Choi E-C, Choi S Y
National Creative Research Initiatives Center for ARS Network, College of Pharmacy, Seoul National University, San 56-1, 151-742 Shillim-dong, Kwanak-gu, Seoul, Korea.
Appl Microbiol Biotechnol. 2003 May;61(4):278-88. doi: 10.1007/s00253-003-1243-5. Epub 2003 Mar 1.
The emergence of multidrug-resistant strains of pathogenic microorganisms and the slow progress in new antibiotic development has led in recent years to a resurgence of infectious diseases that threaten the well-being of humans. The result of many microorganisms becoming immune to major antibiotics means that fighting off infection by these pathogens is more difficult. The best strategy to get around drug resistance is to discover new drug targets, taking advantage of the abundant information that was recently obtained from genomic and proteomic research, and explore them for drug development. In this regard, aminoacyl-tRNA synthetases (ARSs) provide a promising platform to develop novel antibiotics that show no cross-resistance to other classical antibiotics. During the last few years there has been a comprehensive attempt to find the compounds that can specifically target ARSs and inhibit bacterial growth. In this review, the current status in the development of ARS inhibitors will be briefly summarized, based on their chemical structures and working mechanisms.
近年来,致病微生物多重耐药菌株的出现以及新型抗生素研发进展缓慢,导致威胁人类健康的传染病再度流行。许多微生物对主要抗生素产生免疫的结果是,对抗这些病原体感染变得更加困难。克服耐药性的最佳策略是利用最近从基因组和蛋白质组研究中获得的丰富信息发现新的药物靶点,并探索用于药物开发。在这方面,氨酰-tRNA合成酶(ARSs)为开发对其他经典抗生素无交叉耐药性的新型抗生素提供了一个有前景的平台。在过去几年里,人们进行了全面的尝试,以寻找能够特异性靶向ARSs并抑制细菌生长的化合物。在本综述中,将根据ARS抑制剂的化学结构和作用机制简要总结其研发现状。