title: Microtiter plate based chemistry and in situ screening: a useful approach for rapid inhibitor discovery.
abstract: The use of libraries extracted from nature or constructed by combinatorial chemistry, have been widely appreciated in the drug discovery area. In this perspective, we present our contribution to the field of enzyme inhibitor discovery using a useful approach that allows diversification of a common core in a microtiter plate followed by in situ screening. Our method relies on an organic reaction that is highly selective, high yielding, amenable to the microscale and preferably can be performed in water. The core can be a designed molecule based on the structural and mechanistic information of the target, a compound with a weak binding affinity, or a natural product. Several reactions were found useful for this approach and were applied to the rapid discovery of potent inhibitors of representative enzymes.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, USA.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Brik
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Wu
authors.forename: Chi-Huey
authors.initials: CH
authors.lastname: Wong
mesh_terms: D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D017320:HIV Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D017320:HIV Protease Inhibitors; D010447:Peptide Hydrolases