RELATIVE SPECIFICITIES OF A SERIES OF BETA-LACTAM-RECOGNIZING ENZYMES TOWARDS THE SIDE-CHAINS OF PENICILLINS AND OF ACYCLIC THIOLDEPSIPEPTIDES

In an attempt to understand more: of the subtle differences between bacterial beta-lactamases and DD-peptidases. comparisons have been made between the specificities of these enzymes towards the phenylacetyl side chain, generally thought to be favoured by beta-lactamases, and the NN'-diacetyl-L-lysyl side chain, widely employed in low-molecular-mass substrates of DD-peptidases. These comparisons were carried out with both a penicillin and an acyclic thioldepsipeptide reaction nucleus and employing a range of both beta-lactamases and DD-peptidases. Rather contrary to general expectations, a general preference for reaction of both groups of enzymes with penicillins rather than thioldepsipeptides was observed and for the phenylacetyl rather than the NN'diacetyl-L-lysyl side chain. Quantitative comparisons suggested that the side chains of penicillins may be bound in relatively similar sites in all of the enzymes whereas the side chains of thioldepsipeptides are more heterogeneously bound, both with respect to each other and to the comparable side chains of penicillins.