Rational design and synthesis of a highly effective transition state analog inhibitor of the RTEM-1 β-lactamase

Abstract

The synthesis of (1R)-1-acetamido-2-(3-carboxyphenyl)ethane boronic acid , a rationally designed transition state analog competitive inhibitor of the RTEM-1 β-lactamase from Escherichia coli, is reported Kinetic measurements show that, as designed, it is a highly effective reversible inhibitor of the β-lactamase, with an inhibition constant of 110 nM This is the most potent competitive inhibitor of a β-lactamase yet reported.