Aminoacyl-tRNA synthetase inhibitors as potent antibacterials.
The emergence of bacterial strains with resistance to currently marketed antibacterial agents has spurred interest in the discovery of new antibacterial agents with novel modes of action. One set of potential novel targets are the family of bacterial aminoacyltRNA synthetases (AaRS). Aminoacyl-tRNA synthetases are the enzymes that catalyze the transfer of amino acids to their cognate tRNA. They play a pivotal role in protein biosynthesis and are necessary for growth and survival of all cells. Consequently, inhibition of these enzymes is an attractive target for antibacterial agents. In this review, we examine the latest developments and structure-activity relationship (SAR) analysis of aminoacyl-tRNA synthetases inhibitors, including methionyl-tRNA synthetase, isoleucyl-tRNA synthetase and phenylalanyl-tRNA synthetase inhibitors. It is expected that increasing knowledge of the SAR of aminoacyl-tRNA synthetase inhibitors will be beneficial to the rational design of new generation of antibiotics.
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
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D000604:Amino Acyl-tRNA Synthetases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D000604:Amino Acyl-tRNA Synthetases