Basis for the design of anticandidal agents from studies of peptide utilization in Canadida albicans.
The growth of Candida albicans WD 18-4, a methionine and lysine double auxotroph, on a variety of methionine- and lysine-containing peptides was determined. This yeast does not excrete extracellular peptidases. Thus, the growth response to peptides containing the required amino acid is a measure of peptide transport. A variety of methionine-containing peptides such as Met-Met, Met-Met-Met, and Met-Met-Met-Met-Met are transported. Acylation of the N-terminus of transported peptides does not affect their transport, but derivitization of the C-terminus prevents peptide uptake. In contrast, all lysine-containing peptides tested, except Lys-Gly, were not growth substrates. The inability of a peptide to substitute for the requisite amino acid was not due to the absence of cellular peptidases or to toxicity of the nonutilized peptides. Several potentially toxic amino acids were carried into Candida as a component of transported peptides. This establishes the peptide transport system as a possible tool for the design of antibiotics for Candida albicans.
D000935:Antifungal Agents / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002176:Candida albicans / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D008239:Lysine / Q000494:pharmacology; D008715:Methionine / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000378:metabolism; D010455:Peptides / Q000378:metabolism* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D010455:Peptides; D008715:Methionine; D010447:Peptide Hydrolases; D008239:Lysine