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G. V. Lebedev, V. G. Grigorenko, R. L Antipin., M. Yu. Rubtsova, A. M. Egorov
Novel
chromogenic substrate for bacterial beta-lactamases based on cephalosporin
functionalized with epoxy group
Abstract
Beta-lactamases are the key enzymes involved in
resistance towards beta-lactam antibiotics in pathogenic bacteria.
Beta-lactamase inhibitor discovery process and study of resistance mechanisms
force the search for new chromogenic substrates of beta-lactamases. For these
purposes, a novel cephalosporin derivative with an epoxy functional group,
called CMPD1, has been proposed and synthesized. This compound was shown to be
hydrolyzed by TEM type beta-lactamases with a formation of a colored product
with a maximum absorption at 450 nm. The difference in the maximum absorption
of substrate and the product is 95 nm, which exceeds
the value for the substrates previously described. It was found that the CMPD1
compound is hydrolyzed only by TEM type beta-lactamases which do not have
mutations in the active site, which can be used to study the mechanisms of
catalytic action of beta-lactamases.
Key words:
beta-lactamases, chromogenic substrate, cephalosporin, epoxy group, antibiotic
resistance.
Copyright (C) Chemistry Dept., Moscow State University, 2002
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