Activation of antibacterial prodrugs by peptide deformylase

5'-Dipeptidyl derivatives of 5-fluorodeoxyuridine (FdU) (1a-d) were synthes ized. These compounds are biologically inactive but can be activated by pep tide deformylase, which removes the N-terminal formyl group of the dipeptid e, to release the active drug FdU via an intramolecular cyclization reactio n. Because the deformylase is ubiquitous among bacteria but absent in mamma lian cells, 1a-d provide a novel class of potential antibacterial agents. ( C) 2000 Elsevier Science Ltd. All rights reserved.