title: Anticandidal activity of pyrimidine-peptide conjugates.
abstract: The ability of conjugates of peptides and 5-fluorocytosine or 5-fluoroorotic acid to enter Candida albicans was investigated. A number of conjugates of 5-fluoroorotic acid and peptides were synthesized using 1-(ethoxy-carbonyl)-2-ethoxy-1,2-dihydroquinoline as the coupling agent. Orotyl-L-leucyl-L-leucine, 5-fluoro-4-(N-succinamoyl-L-alanyl-L-leucine)-2(1H)-pyrimidinone [a 5-fluorocytosine derivative], and 5-fluoroorotyl-L-leucyl-L-leucine all inhibited the uptake of trimethionine into C. albicans WD 18-4. Inhibition by 5-fluoroorotyl-L-leucyl-L-leucine was competitive as judged using double-reciprocal plots. Evaluation of minimum inhibitory concentrations of peptide-5-fluorocytosine conjugates suggest that these conjugates enter C. albicans in the intact form. These results provide the first experimental evidence that peptides can carry pyrimidines into a eukaryote.
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000378:metabolism; D001692:Biological Transport; D002176:Candida albicans / Q000187:drug effects* / Q000378:metabolism; D009963:Orotic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis; D010455:Peptides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000187:drug effects
chemical_list: D000935:Antifungal Agents; D010455:Peptides; D011743:Pyrimidines; D009963:Orotic Acid