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Enzymatic Transition States and Drug Design.

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.

SUBMITTER: Schramm VL

PROVIDER: S-EPMC6615489 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Enzymatic Transition States and Drug Design.

Schramm Vern L VL

Chemical reviews 20181018 22

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 transit ...[more]

PMID: 30335982

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