Chemical Specificity of thePDR5Multidrug Resistance Gene Product ofSaccharomyces cerevisiaeBased on Studies with Tri-n-Alkyltin Chlorides

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Abstract
To understand the chemical basis of action for thePDR5-encoded multidrug resistance transporter ofSaccharomyces cerevisiae, we compared the relative hypersensitivities of the wild-type (RW2802) and null mutant strains toward a series of tri-n-alkyltin compounds. These compounds differ from each other in a systematic fashion—either by hydrocarbon chain length or by anion composition. Using zone-of-inhibition and fixed-concentration assays, we found that the ethyl, propyl, and butyl compounds are strongPDR5substrates, whereas the methyl and pentyl compounds are weak. We conclude that hydrophobicity and anion makeup are relatively unimportant factors in determining whether a tri-n-alkyltin compound is a goodPDR5substrate but that the dissociation of the compound and the molecular size are significant.

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