The use of ribosomal crystal structures in antibiotic drug design.

The ribosome is one of the richest validated targets for antibacterial drug discovery. In combination with advances in computational and biological methods, the determination of ribosomal structures with bound substrates and inhibitors has launched a new era in the structure-based drug design (SBDD) of novel antibacterials. This review discusses the oxazolidone class of compounds, which has been the focus of most of the ribosome-targeted SBDD disclosed in the last 3 years; such SBDD has led to significant improvements in the potency and spectrum of activity of these compounds. Recent SBDD results for the aminoglycosides are also summarized, and ribosome-targeted compounds in clinical trials are reviewed. The encouraging results described support the future use of ribosomal SBDD in the development of antibiotic compounds.