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. 1982 Sep;22(3):414–420. doi: 10.1128/aac.22.3.414

Interaction of azthreonam and related monobactams with beta-lactamases from gram-negative bacteria.

K Bush, J S Freudenberger, R B Sykes
PMCID: PMC183759  PMID: 6982680

Abstract

Monobactams containing 3 beta-aminothiazolyl oxime side chains (SQ 81,377, SQ 81,402, azthreonam, and SQ 26,917) have poor affinities for the broad-spectrum beta-lactamases TEM-2 and K1. Addition of a 4-methyl substituent significantly increased stability to hydrolysis by these enzymes. P99 cephalosporinase from Enterobacter cloacae was strongly inhibited by the monobactams. Interaction of azthreonam with the P99 enzyme in equimolar concentrations resulted in a single covalent complex which retained less than 3% catalytic activity. On incubation, enzymatic activity was slowly regained. Chromatographic studies of the incubation mixtures revealed the presence of a single ring-opened product. It is concluded that monobactams act as poor substrates for broad-spectrum beta-lactamases and tight-binding competitive substrates for the P99 beta-lactamase.

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Selected References

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