Development of a FRET-based High-Throughput Screening System for the Discovery of Hsp90 Inhibitors

摘要

A FRET-based high-throughput screening system was developed for the discovery of competitive small-molecule Hsp90 inhibitors. The biarsenical fluorescein derivative FlAsH and dabcyl-conjugated Hsp90 inhibitor GM were employed as the FRET donor and quencher, respectively. The spatial proximity perturbation between FlAsH-labeled Hsp90N and GM-dabcyl upon treatment of a small molecule led to changes in the FRET-induced fluorescence, monitored in a high-throughput fashion.