Penicillins as beta-lactamase-dependent prodrugs: enabling role of a vinyl ester exocyclic to the lactam ring.
Incorporation of a vinyl ester exocyclic to the beta-lactam ring of a penicillin nucleus enables this to act as a beta-lactamase-dependent prodrug - rapid release of the (unactivated) alkoxy component of the vinyl ester is triggered by enzyme-catalysed hydrolysis of the beta-lactam ring, whilst buffer-catalysed hydrolysis of the structure at neutral pH is particularly slow.
Ruddle
Carol C
CC
Department of Chemical and Environmental Sciences, University of Limerick, Ireland.
Smyth
Timothy P
TP
D006863:Hydrogen-Ion Concentration; D007769:Lactams / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D010406:Penicillins / Q000737:chemistry*; D011355:Prodrugs / Q000737:chemistry*; D014753:Vinyl Compounds / Q000737:chemistry; D001618:beta-Lactamases / Q000737:chemistry*
D007769:Lactams; D010406:Penicillins; D011355:Prodrugs; D014753:Vinyl Compounds; D001618:beta-Lactamases