Aminoacyl tRNA synthetases as targets for new anti-infectives

被引:155
作者
Schimmel, P
Tao, JS
Hill, J
机构
[1] Scripps Res Inst, Skaggs Inst Chem Biol, Beckman Ctr, La Jolla, CA 92037 USA
[2] Cubist Pharmaceut Inc, Cambridge, MA 02139 USA
关键词
antibiotic resistance; translation apparatus; pathogen-specific inhibitor; vancomycin; mainline antibiotics;
D O I
10.1096/fasebj.12.15.1599
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Because resistance has developed to mainline antibiotics, including vancomycin, new antibiotics are now being aggressively sought, For this purpose, aminoacyl tRNA synthetases are being pursued as targets for new drug, These enzymes are universal and are essential for cell viability. The key to their usefulness lies in being able to find drugs that inhibit a pathogen synthetase but not its human cell. counterpart. The possibility for species-specific inhibition was originally demonstrated with a natural product and has now been demonstrated with prototypical drug that are based on the structure of an intermediate of the aminoacylation reaction. Efficacy of a rationally designed inhibitor has been shown in vivo with a pathogen infection established in an animal model, Although many challenges remain, these early results suggest that synthetases will continue to be of major interest for development of new anti-infectives.
引用
收藏
页码:1599 / 1609
页数:11
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