High-throughput identification of promiscuous inhibitors from screening libraries with the use of a thiol-containing fluorescent probe.

ABSTRACT: Testing small molecules for their ability to modify cysteine residues of proteins in the early stages of drug discovery is expected to accelerate our ability to develop more selective drugs with lesser side effects. In addition, this approach also enables the rapid evaluation of the mode of binding of new drug candidates with respect to thiol reactivity and metabolism by glutathione. Herein, we describe the development of a fluorescence-based high-throughput assay that allows the identification of thiol-reactive compounds. A thiol-containing fluorescent probe, MSTI, was synthesized and used to evaluate small molecules from the Library of Pharmacologically Active Compounds (LOPAC) collection of bioactive molecules. LOPAC compounds that are known to react with sulfur nucleophiles were identi

SUBMITTER: McCallum MM 

PROVIDER: S-EPMC3692575 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature