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

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