State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
Curr Med Chem. 2012;19(21):3550-63. doi: 10.2174/092986712801323199.
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.
细菌菌株对目前市售抗菌药物的耐药性的出现，刺激了人们对具有新型作用模式的新型抗菌药物的发现产生了兴趣。一组潜在的新型靶标是细菌氨酰-tRNA 合成酶（AaRS）家族。氨酰-tRNA 合成酶是催化氨基酸转移到其相应 tRNA 的酶。它们在蛋白质生物合成中起着关键作用，是所有细胞生长和存活所必需的。因此，抑制这些酶是抗菌药物的一个有吸引力的靶标。在这篇综述中，我们研究了氨酰-tRNA 合成酶抑制剂的最新进展和结构活性关系（SAR）分析，包括甲硫氨酰-tRNA 合成酶、异亮氨酰-tRNA 合成酶和苯丙氨酰-tRNA 合成酶抑制剂。预计增加对氨酰-tRNA 合成酶抑制剂 SAR 的了解将有助于新一代抗生素的合理设计。
