Novel mechanism of inhibiting beta-lactamases by sulfonylation using beta-sultams

Michael I Page; Paul S Hinchliffe; J Matthew Wood; Lindsay P Harding; Andrew P Laws

doi:10.1016/j.bmcl.2003.08.082

Novel mechanism of inhibiting beta-lactamases by sulfonylation using beta-sultams

Bioorg Med Chem Lett. 2003 Dec 15;13(24):4489-92. doi: 10.1016/j.bmcl.2003.08.082.

Authors

Michael I Page¹, Paul S Hinchliffe, J Matthew Wood, Lindsay P Harding, Andrew P Laws

Affiliation

¹ Department of Chemical and Biological Sciences, The University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK. m.i.page@hud.ac.uk

PMID: 14643353
DOI: 10.1016/j.bmcl.2003.08.082

Abstract

Beta-sultams are the sulfonyl analogues of beta-lactams and N-acyl beta-sultams are novel inactivators of the class C beta-lactamase of Enterobacter cloacae P99. The rates of inactivation show a similar pH-rate dependence as that exhibited by the beta-lactam antibiotics and with ESIMS data it is suggested that beta-sultams sulfonylate the active site serine residue to form a sulfonate ester.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Enterobacter cloacae / enzymology
Enzyme Inhibitors / pharmacology*
Hydrogen-Ion Concentration
Kinetics
Structure-Activity Relationship
Sulfonamides / chemical synthesis
Sulfonamides / chemistry
Sulfonamides / pharmacology*
Sulfones
beta-Lactamase Inhibitors*

Substances

Enzyme Inhibitors
Sulfonamides
Sulfones
beta-Lactamase Inhibitors
beta-sultam