Work

Transition States, Analogues, and Drug Development

Year: 2012

Type: article

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.

Source: ACS Chemical Biology

DOI: 10.1021/cb300631k

Author: Vern L. Schramm

Institution: Albert Einstein College of Medicine

Language: English

Topic: Chemical Reaction Mechanisms

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases