Novel mechanism of inhibiting beta-lactamases by sulfonylation using beta-sultams.
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.
Page
Michael I
MI
Department of Chemical and Biological Sciences, The University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK. m.i.page@hud.ac.uk
Hinchliffe
Paul S
PS
Wood
J Matthew
JM
Harding
Lindsay P
LP
Laws
Andrew P
AP
D016972:Enterobacter cloacae / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013450:Sulfones; D065093:beta-Lactamase Inhibitors
D004791:Enzyme Inhibitors; D013449:Sulfonamides; D013450:Sulfones; D065093:beta-Lactamase Inhibitors; C480101:beta-sultam