STRUCTURE-ACTIVITY-RELATIONSHIPS OF PENEM ANTIBIOTICS - CRYSTALLOGRAPHIC STRUCTURES AND IMPLICATIONS FOR THEIR ANTIMICROBIAL ACTIVITIES

Twelve closely related crystal structures of the penem derivatives rev ealed a characteristic short contact of the oxygen atom in the C2 side -chains with the S1 atom. The side-chain conformations of the crystal structures showed a good correlation with the antimicrobial activity. In particular, the penems which show high antimicrobial activity have similar torsion angles for S1-C2-C1'-C2', suggesting that the disposit ion of the C2' atom would be important for binding to penicillin-inter acting enzymes. Two conformations of the C6 hydroxyethyl group were ob served in the crystal structures. Of those two, the conformation with a larger torsion angle (delta = 179.2 degrees) is deduced to be the en zyme-bound conformation in the Michaelis complex. (C) 1997 Elsevier Sc ience Ltd.