title: High-throughput screening of enzyme inhibitors: automatic determination of tight-binding inhibition constants.
abstract: Determination of tight-binding inhibition constants by nonlinear least-squares regression requires sufficiently good initial estimates of the best-fit values. Normally an initial estimate of the inhibition constant must be provided by the investigator. This paper describes an automatic procedure for the estimation of tight-binding inhibition constants directly from dose-response data. Because the procedure does not require human intervention, it was incorporated into an algorithm for high-throughput screening of enzyme inhibitors. A suitable computer program is available electronically (http://www.biokin.com). Representative experimental data are shown for the inhibition of human mast-cell tryptase.
authors.affiliation: BioKin, Ltd., Madison, Wisconsin 53708, USA. pkuzmic@biokin.com
authors.forename: P
authors.initials: P
authors.lastname: Kuzmic
authors.forename: S
authors.initials: S
authors.lastname: Sideris
authors.forename: L M
authors.initials: LM
authors.lastname: Cregar
authors.forename: K C
authors.initials: KC
authors.lastname: Elrod
authors.forename: K D
authors.initials: KD
authors.lastname: Rice
authors.forename: J W
authors.initials: JW
authors.lastname: Janc
mesh_terms: D000465:Algorithms; D001331:Automation; D001667:Binding, Competitive; D053818:Chymases; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000032:analysis* / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D009010:Monte Carlo Method; D012697:Serine Endopeptidases / Q000187:drug effects / Q000378:metabolism*; D053802:Tryptases
chemical_list: D004791:Enzyme Inhibitors; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases