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.
Wei
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Y
Department of Chemistry and Ohio State Biochemistry Program, The Ohio State University, Columbus 43210, USA.
Pei
D
D
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
D000900:Anti-Bacterial Agents; D011355:Prodrugs; D005467:Floxuridine; D000626:Aminopeptidases; D000581:Amidohydrolases; C084507:peptide deformylase