On the structural analogy between D-alanyl-D-alanine terminated peptides and β-lactam antibiotics

Structural analogy between D-alanyl-D-alanine terminated peptides (and analogues) of varying substrate activity toward D-alanyl-D-alanine-cleaving peptidases, and bicyclic fused ring azetidinone structures of varying inactivating potency toward the same enzymes has been exa-mihed by comparing the relative spatial disposition of the carboxylate function at the C-terminal position and the amide function at the N-terminal position with respect to the scissile amide bond at the central position. The observed variations in the geometric parameters and the molecular electrostatic potential maps generated by these functional groups suggest multiple modes of binding. In the monobactam sulfazecin, the relative disposition of at least the scissile amide bond and the terminal sulphamate group is comparable to that of the corresponding functions in the bicyclic β-lactams.