Targeting metalloenzymes: a strategy that works

Abstract

Faced with a wealth of antibacterial drug discovery targets as a result of bacterial genomics, we need to carefully select which ones to work with. Choosing bacterial metalloenzymes is one possible approach that can increase the probability of success. Metalloenzymes can be identified through specific motif searches of bacterial genomes. Current state-of-the-art medicinal chemistry allows for the design of inhibitor libraries targeting metalloenzymes and the efficient optimization of leads identified. This approach has been successfully applied to the discovery of in vivo active antibacterial agents that are inhibitors of bacterial peptide deformylase and UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase. Other bacterial metalloenzymes are open to the same approach.