Chemical Specificity of the PDR5 Multidrug Resistance Gene Product of Saccharomyces cerevisiae Based on Studies with Tri-n-Alkyltin Chlorides

To understand the chemical basis of action for the PDR5-encoded multidrug resistance transporter of Saccharomyces 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 strong PDR5 substrates, 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 good PDR5 substrate but that the dissociation of the compound and the molecular size are significant.