Transition states, analogues, and drug development

Research output: Contribution to journalArticle

74 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)71-81
Number of pages11
JournalACS Chemical Biology
Volume8
Issue number1
DOIs
StatePublished - Jan 18 2013

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Computational chemistry
Enzymes
Thermodynamics
Isotopes
Pharmaceutical Preparations
Conformations
Kinetics
Geometry
Substrates

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Cite this

Transition states, analogues, and drug development. / Schramm, Vern L.

In: ACS Chemical Biology, Vol. 8, No. 1, 18.01.2013, p. 71-81.

Research output: Contribution to journalArticle

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