Relative rates of transport of peptidyl drugs by Candida albicans

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Abstract
A variety of peptide drugs are known to be active against Candida albicans; however, little is known about the transport of such agents into the target organism. To provide further information concerning transport of this type, we studied the uptake of two classes of small linear peptides: polyoxins which act intact within the cell and the m-fluorophenylalanyl (m-F-Phe) peptides which require peptidase cleavage to release m-F-Phe. Competition studies with a specific dipeptide detector (alanyl-alpha-thiophenylglycine) enabled us to determine Ki values of 2.6 microM for nikkomycin Z and 350 microM for polyoxin D. Rates of uptake of the peptidyl-nucleosides are approximately 30 times lower than those of the m-F-Phe peptides (apparent maximal velocities: nikkomycin Z, 62 pmol min-1 mg (dry weight) of cells-1; M-F-Phe alanine 1.3 nmol min-1 mg (dry weight) of cells-1). For both the m-F-Phe peptides and the peptidyl-nucleosides, the affinity of the drug for the transport system is an important determinant of its whole-cell activity.