Inactivation of the RTEM .beta.-lactamase from Escherichia coli. Interaction of penam sulfones with the enzyme

Abstract
The characteristics of the reaction of a number of mechanism-based inactivators of RTEM .beta.-lactamase from E. coli have suggested that a common mechanistic pathway may be followed by many of these compounds. These ideas were tested by the synthesis and evaluation of some penam sulfones as .beta.-lactamase inactivators. The sulfones of poor .beta.-lactamase substrates are, as predicted, potent inactivators of the enzyme. A unique serine residue (Ser-70) is labeled by quinacillin sulfone and it is likely that this serine acts nucleophilically in the normal hydrolytic reaction of the .beta.-lactamase to form an acyl-enzyme intermediate.