High-Throughput Solid-Phase Synthesis of Nucleoside-Based Libraries in the Search for New Antibiotics

Acknowledgments .......................................................................................................................... 236 References ...................................................................................................................................... 236

There is an urgent need for the development of novel, more effective antibiotic drugs, with new mechanisms of action to combat emerging drug-resistant bacterial pathogens such as penicillinresistant Streptococcus pneumoniae, vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, multi-drug-resistant Mycobacterium tuberculosis, Pseudonomas aeruginosa,

and Acinetobacter baumanii.1 The recent advent of genomic and proteomic sciences has led to the discovery of many new potential targets; however, few of these targets when screened have produced suitable lead candidates.2 An equally attractive approach to lead identification in the early stages of the drug discovery process is to screen new chemical classes of compounds, often based around natural product templates, in phenotypic screens, followed by the application of genomics strategies to determine the exact target. This approach is particularly applicable to the discovery of new antimicrobial agents.