Epoxide Opening in Water and Screening in Situ for Rapid Discovery of Enzyme Inhibitors in Microtiter Plates

A method utilizing the strategy of epoxide opening by amine with water as co-solvent and screening in situ was developed for rapid discovery of protein inhibitors. Using this approach, HIV protease inhibitors with novel P1' residues were identified in our study. This strategy should be applicable for the efficient assembly of diverse compound collections for inhibitors' discovery and optimization in other systems.