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PMID: 2983675 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Inhibition of class C beta-lactamases by (1'R,6R)-6-(1'-hydroxy)benzylpenicillanic acid SS-dioxide.

The Biochemical journal ·Vol. 225 ·No. 2 ·1985-01-15 ·Pages 435-9

Knight GC, Waley SG

Abstract

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.

MeSH Terms
Cephalosporins/metabolism Hydrogen-Ion Concentration Hydroxylamine Hydroxylamines/pharmacology Kinetics Penicillanic Acid/pharmacology Pseudomonas aeruginosa/enzymology Spectrophotometry beta-Lactamase Inhibitors
Chemicals
Cephalosporins Hydroxylamines beta-Lactamase Inhibitors Hydroxylamine cephalosporin C 6-(1-hydroxy)benzylpenicillanic acid S,S-dioxide Penicillanic Acid
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Knight G C
Waley S G
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22 references, click to expand
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj2250435
Published
1985-01-15
Pages
435-9
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1144608
Subset
IM
External Links
PubMed source DOI: 10.1042/bj2250435 PMC Full Text View journal details
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