Development of New Antibiotics

We will develop new antibiotics based on the inhibition of pathogen protein synthesis through a preunexplored mechanism. The aminoacyl tRNA synthetases (AARS), a family of enzymes that catalyze the fprotein translation, will be targeted. The investigators will exploit the significant selectivity shpathogen cells exhibited by lead structures that have been selected for the study. This will provideachieve species specific inhibition and, therefore, minimize toxicity to human cells. The proposal hdevelop inhibitors of isoleucyl tRNA synthetase with improved stability, potency and expanded antibasuitable for oral or intra venous route of administration; 2) to probe the binding mode of PMA-A andisoleucyl tRNA synthetase through rationally designed hybrid molecules. The synthetic compounds willdetermine potency. The active compounds will then be tested against a range of bacterial and fungalcell assay. The investigators will also specifically test for activities against Mycobacterium tubercarinii.