Vern L Schramm1. 1. Department of Biochemistry , Albert Einstein College of Medicine , 1300 Morris Park Avenue , Bronx , New York 10461 , United States.
Abstract
Transition state theory teaches that chemically stable mimics of enzymatic transition states will bind tightly to their cognate enzymes. Kinetic isotope effects combined with computational quantum chemistry provides enzymatic transition state information with sufficient fidelity to design transition state analogues. Examples are selected from various stages of drug development to demonstrate the application of transition state theory, inhibitor design, physicochemical characterization of transition state analogues, and their progress in drug development.
Transition state theory teaches that chemically stable mimics of enzymatic transition states will bind tightly to their cognate enzymes. Kinetic isotope effects combined with computational quantum chemistry provides enzymatic transition state information with sufficient fidelity to design transition state analogues. Exn class="Chemical">amples are selected from various stages of drug development to demonstrate the application of transition state theory, inhibitor design, physicochemical characterization of transition state analogues, and their progress in drug development.
Authors: Xin Chen; Stephan Schauder; Noelle Potier; Alain Van Dorsselaer; István Pelczer; Bonnie L Bassler; Frederick M Hughson Journal: Nature Date: 2002-01-31 Impact factor: 49.962
Authors: W Montfort; J E Villafranca; A F Monzingo; S R Ernst; B Katzin; E Rutenber; N H Xuong; R Hamlin; J D Robertus Journal: J Biol Chem Date: 1987-04-15 Impact factor: 5.157
Authors: Minyoung Kevin Kim; Aishan Zhao; Ashley Wang; Zachary Z Brown; Tom W Muir; Howard A Stone; Bonnie L Bassler Journal: Nat Microbiol Date: 2017-05-22 Impact factor: 17.745
Authors: Erin L Higgins; Julian S Kellner-Rogers; Alexandra M Estanislau; Alec C Esposito; Nora R Vail; Sterling R Payne; Julia G Stockwell; Scott M Ulrich Journal: Bioorg Med Chem Lett Date: 2021-02-23 Impact factor: 2.823
Authors: Vinardas Kelpšas; Octav Caldararu; Matthew P Blakeley; Nicolas Coquelle; Rikkert K Wierenga; Ulf Ryde; Claes von Wachenfeldt; Esko Oksanen Journal: IUCrJ Date: 2021-06-03 Impact factor: 4.769