β-Lactamase-Dependent Prodrugs—Recent Developments

Penicillins and cephalosporins bearing an S-aminosulfenimine side chain at the 6- and 7-positions, respectively, are prototypic examples of novel classes of β-lactamase-dependent prodrugs wherein enzyme-catalyzed cleavage of the β-lactam ring triggers the rapid expulsion of the S-amino moiety. The cephalosporin structure behaves as a dual-release prodrug as here release of both the S-amino moiety and of the 3′-substituent occurs sequentially following cleavage of the β-lactam ring. This reaction pattern constitutes an enabling technology at the molecular level and has potential application in antibody-directed enzyme prodrug therapy (ADEPT) and in the further development of β-lactamase-dependent prodrugs for use as antibiotics.