A study of drug-peptide conjugates against the opportunistic yeast CANDIDA ALBICANS

A series of orotyl and fluoroorotyl-peptides were tested as possible drugs against the opportunistic yeast Candida albicans. None of the peptides were toxic; however, two seemed to be transported into the cells, based on competition of transport assays with radioactive peptide trimethionine. The most promising of the drug-peptides, fluoroorotyl-leucyl-leucine, was a competitive inhibitor By this criterion fluoroorotyl-leucyl-leucine seemed to be getting into the cells through the oligopeptide transport system. It was shown that even though fluoroorotyl-leucylleucine was transported into cells, it was not toxic because the drug, fluoroorotic acid, was not released from the peptide. Fluoroorotic acid, by itself, was inhibitory to the pyrimidine biosynthetic enzyme activities of the yeast cell. It was concluded that fluoroorotic acid is carried into cells via the oligopeptide transport system and if fluoroorotic acid were released from the peptide, it should be inhibitory to the enzymes of the yeast. This was the first instance that a fluorinated pyrimidine was shown to be carried into cells by way of the oligopeptide permease.