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 r esistance transporter of Saccharomyces cerevisiae, me compared the relative hypersensitivities of the wild-type (RW2802) and null mutant strains towar d a series of tri-n-alkyltin compounds. These compounds differ from each ot her in a systematic fashion-either by hydrocarbon chain length or by anion composition. Using zone-of-inhibition and fixed-concentration assays, me fo und that the ethyl, propyl, and butyl compounds are strong PDR5 substrates, whereas the methyl and pentyl compounds are weak. We conclude that hydroph obicity and anion makeup are relatively unimportant factors in determining whether a tri-n-alkyltin compound is a goad PDR5 substrate but that the dis sociation of the compound and the molecular size are significant.