title: Activation of antibacterial prodrugs by peptide deformylase.
abstract: 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.
authors.affiliation: Department of Chemistry and Ohio State Biochemistry Program, The Ohio State University, Columbus 43210, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Wei
authors.forename: D
authors.initials: D
authors.lastname: Pei
mesh_terms: D000581:Amidohydrolases; D000626:Aminopeptidases / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D015195:Drug Design; D004355:Drug Stability; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D005467:Floxuridine / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D011355:Prodrugs / Q000737:chemistry* / Q000378:metabolism; D013212:Staphylococcus epidermidis / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D011355:Prodrugs; D005467:Floxuridine; D000626:Aminopeptidases; D000581:Amidohydrolases; C084507:peptide deformylase