The identification of quality antibacterial drug discovery targets: a case study with aminoacyl-tRNA synthetases

Abstract

Although there is a clearly established need for new antibiotics, the route to their discovery is anything but clear or defined. One possible approach is target-based drug discovery. Adhering to this strategy, appropriate targets must first be selected. Even this early stage step in the process is not straightforward. As described here, numbers of genomics targets are available and a subset of those have been linked to infection. However, only a further subset of these targets will prove amenable to drug discovery. Here we profile two approaches to identify quality drug discovery targets from within a family of enzymes known as aminoacyl-tRNA synthetases. Targets were selected based on (i) high throughput screening data or (ii) protein sequence similarity analyses. The merits of each approach are discussed. Although some measure of success was achieved using sequence similarity to prioritise targets, high throughput screening data and the subsequent profiling of hits resulted in the selection of higher quality targets for further study.

• aminoacyl-tRNA synthetases
• antibiotics
• high throughput screening
• protein sequence homology
• quality targets
• target-based drug discovery