Inhibition of class C beta-lactamases by (1'R,6R)-6-(1'-hydroxy)benzylpenicillanic acid SS-dioxide.
beta-Lactamases, enzymes that catalyse the hydrolysis of the beta-lactam ring in beta-lactam antibiotics, are divided into three classes, A, B and C, on the basis of the structures so far determined. There are relatively few effective inhibitors of class C beta-lactamases. A beta-lactam sulphone with a hydroxybenzyl side chain, namely (1'R,6R)-6-(1'-hydroxy)benzylpenicillanic acid SS-dioxide (I), has now been studied. The sulphone is a good mechanism-based inhibitor of class C beta-lactamases. At pH8, the inhibition of a Pseudomonas beta-lactamase is irreversible, and proceeds at a rate that is about one-tenth the rate of concurrent hydrolysis. The labelled enzyme has enhanced u.v. absorption and is probably an enamine. At a lower pH, however, inhibition is transitory.
Knight
G C
GC
Waley
S G
SG
D002511:Cephalosporins / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D019811:Hydroxylamine; D006898:Hydroxylamines / Q000494:pharmacology; D007700:Kinetics; D010397:Penicillanic Acid / Q000494:pharmacology* / Q000031:analogs & derivatives; D011550:Pseudomonas aeruginosa / Q000201:enzymology; D013053:Spectrophotometry; D065093:beta-Lactamase Inhibitors
D002511:Cephalosporins; D006898:Hydroxylamines; D065093:beta-Lactamase Inhibitors; D019811:Hydroxylamine; C025163:cephalosporin C; C044381:6-(1-hydroxy)benzylpenicillanic acid S,S-dioxide; D010397:Penicillanic Acid