Synthesis of the dodecapeptide-alpha mating factor of Saccharomyces cerevisiae

The synthesis of His-Trp-Leu-Gln-Leu-Lys-Pro-Gly-Gln-Pro-Met-Tyr, the dodecapeptide alpha-mating factor from Saccharomyces cerevisiae, and its Ala2- and Cha2-(beta-cyclohexylalanine) analogs are reported. Peptides were synthesized in solution using a combination of mixed anhydride and 1-hydroxybenzotriazole accelerated active ester coupling procedures. Dilute methanesulfonic acid (0.1-0.2 M) in methylene chloride-formic acid solution was employed to specifically remove the tert.-butoxycarbonyl group in the presence of the benzyloxycarbonyl group. Free peptides were obtained using catalytic transfer hydrogenation with formic acid as the hydrogen donor followed by mild acidolysis with trifluoroacetic acid. The alpha-factor and the Cha2-analog exhibited almost equal ability to cause "shmooing" of a-mating types of S. cerevisiae whereas the Ala2-analog exhibited no activity in this assay. These results differ with structure-activity studies reported on the tridecapeptide alpha-factor.