Dr. Michael Charlton and Dr. Grace Edmund recently reported our work in the design of novel compounds to target the synthetic active site of Leucyl-tRNA synthetase (LeuRS), responsible for the aminoacylation reaction. The critical role of this site presents a significant barrier to the development of viable mutations and makes it an attractive target for antibacterial drug discovery.
Our presentation showcased our low molecular weight series of inhibitors that bind strongly to LeuRS without the need for an adenosine mimic. The compounds are good inhibitors of Gram-negative enzymes and have promising antimicrobial activity.
We also presented a poster outlining our work on using the Molecular Mechanics/Generalized Born – Volume Integral (MM/GB-VI) approach to predict ligand-protein binding affinities for a set of E. coli LeuRS inhibitors.