Approaches to antibacterial drug discovery.
The discovery of new antibacterial drugs can be based either upon empirical screening methods or structure-based design. Empirical methods utilise both intact bacteria and isolated biochemical targets for high throughput screening of natural product or chemical libraries to detect inhibitor leads. Structure-based methods for drug design are based upon understanding the molecular architecture of the active site in an appropriate target molecule. Empirical methods have been widely applied to screen for antibacterial agents and the introduction of combinatorial methods for the synthesis of chemical libraries considerably expands the potential of empirical screening methods. In contrast, structure-based drug design has not yet been widely applied to the development of antibacterial drugs, although it has proved to be a successful approach in other therapeutic areas. Recent advances in the sequencing of bacterial genomes will assist both empirical and structure-based approaches by identifying new, essential bacterial genes whose products may become the targets of new agents with selective antibacterial activity.
Antimicrobial Research Centre and Department of Microbiology, University of Leeds, Leeds, LS2 9JT, UK.
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