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. 1991 May 1;275(Pt 3):793–795. doi: 10.1042/bj2750793

Phosphonate monoester inhibitors of class A beta-lactamases.

J Rahil 1, R F Pratt 1
PMCID: PMC1150124  PMID: 1903928

Abstract

Phosphonate monoesters with the general structure: [formula: see text] are inhibitors of representative class A and class C beta-lactamases. This result extends the range of this type of inhibitor to the class A enzymes. Compounds where X is an electron-withdrawing substituent are better inhibitors than the unsubstituted analogue (X = H), and enzyme inhibition is concerted with stoichiometric release of the substituted phenol. Slow turnover of the phosphonates also occurs. These observations support the proposition that the mechanism of action of these inhibitors involves phosphorylation of the beta-lactamase active site. The inhibitory ability of these phosphonates suggests that the beta-lactamase active site is very effective at stabilizing negatively charged transition states. One of the compounds described also inactivated the Streptomyces R61 D-alanyl-D-alanine carboxypeptidase/transpeptidase.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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