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Transition States, analogues, and drug development.

ABSTRACT: Enzymes achieve their transition states by dynamic conformational searches on the femtosecond to picosecond time scale. Mimics of reactants at enzymatic transition states bind tightly to enzymes by stabilizing the conformation optimized through evolution for transition state formation. Instead of forming the transient transition state geometry, transition state analogues convert the short-lived transition state to a stable thermodynamic state. Enzymatic transition states are understood by combining kinetic isotope effects and computational chemistry. Analogues of the transition state can bind millions of times more tightly than substrates and show promise for drug development for several targets.

SUBMITTER: Schramm VL

PROVIDER: S-EPMC3560411 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Transition States, analogues, and drug development.

Schramm Vern L VL

ACS chemical biology 20130104 1

Enzymes achieve their transition states by dynamic conformational searches on the femtosecond to picosecond time scale. Mimics of reactants at enzymatic transition states bind tightly to enzymes by stabilizing the conformation optimized through evolution for transition state formation. Instead of forming the transient transition state geometry, transition state analogues convert the short-lived transition state to a stable thermodynamic state. Enzymatic transition states are understood by combin ...[more]

PMID: 23259601

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