Aminoacyl-tRNA synthetases and their inhibitors as a novel family of antibiotics.
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.
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. sungkim@snu.ac.kr
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D000604:Amino Acyl-tRNA Synthetases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D018716:Molecular Mimicry; D016712:Mupirocin / Q000031:analogs & derivatives / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D016712:Mupirocin; D000604:Amino Acyl-tRNA Synthetases