title: The development of molecular clamps as drugs.
abstract: Some enzymes catalyze the modification of an ensemble of substrates in vivo and, as a consequence, are not ideal targets for active-site-directed drugs. One solution to inhibiting such multisubstrate enzymes would be a drug that binds tightly to only one substrate, which prevents the binding of that substrate to the enzyme. Ideally, such a drug (called a molecular clamp, a molecular forcep or a molecular tweezer) would prevent the enzymatic processing of only the targeted substrate. This would enable the enzyme to function normally on all other substrates. Here, we review the unique steady-state kinetic features of molecular clamp inhibition, identify potential targets for molecular clamp inhibition, and discuss problems for the therapeutic use of molecular clamps.
authors.affiliation: Departments of Chemistry and Interdisciplinary Oncology, University of South Florida, 4202 E. Fowler Ave. CHE 205, Tampa, FL 33620, USA.
authors.forename: Stephanie T
authors.initials: ST
authors.lastname: Weiss
authors.forename: Neil R
authors.initials: NR
authors.lastname: McIntyre
authors.forename: Mark L
authors.initials: ML
authors.lastname: McLaughlin
authors.forename: David J
authors.initials: DJ
authors.lastname: Merkler
mesh_terms: D016503:Drug Delivery Systems; D015195:Drug Design; D004791:Enzyme Inhibitors; D004798:Enzymes / Q000378:metabolism; D006801:Humans; D013379:Substrate Specificity
chemical_list: D004791:Enzyme Inhibitors; D004798:Enzymes