Anticandidal activity of pyrimidine-peptide conjugates

Article abstract of DOI:10.1021/jm00182a019

The ability of conjugates of peptides and 5-fluorocytosine or 5-fluoro-ortic acid to enter 'Candida albicans' was investigated. A number of conjugates of 5-fluoro-orotic acid and peptides were synthesized using 1-(ethoxycarbonyl)-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-fluoro-orotyl-L-leucyl-L-leucine all inhibited the uptake of trimethionine into 'C. albicans' WD 18-4. Inhibition by 5-fluoro-orotyl-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.