Activation of antibacterial prodrugs by peptide deformylase

5′-Dipeptidyl derivatives of 5-fluorodeoxyuridine (FdU) (1a–d) were synthesized. These compounds are biologically inactive but can be activated by peptide deformylase, which removes the N-terminal formyl group of the dipeptide, to release the active drug FdU via an intramolecular cyclization reaction. Because the deformylase is ubiquitous among bacteria but absent in mammalian cells, 1a–d provide a novel class of potential antibacterial agents.