Chu-Biao Xue

Total synthesis of the lipopeptide a-mating factor ofSaccharomyces cerevisiae

The a-mating factor of Saccharomyces cerevisiae was synthesized using both solution phase and solid phase strategies. Structure of the final peptide was confirmed using amino acid analysis, fast atom bombardment mass spectroscopy and 400 MHz proton NMR. The synthetic farnesylated dodecapeptide, YIIKGVFWDPAC (S-farnesyl) OCH3, exhibited chromatographic and spectroscopic properties identical to the natural pheromone and had significant biological activity at nanomolar concentrations.

The conformation of a-factor is not influenced by the S-prenylation of Cys12

Two-Dimensional NMR was used to examine the solution conformation of the lipopeptide a-factor, YIIKGVFWDPAC (S-farnesyl) OCH3, from the yeast Saccharomyces cerevisiae and five analogues containing various S-alkylated cysteines in DMSO-d6. NOESY data, NH temperature coefficients, and 3J alpha NH coupling constants indicate that the a-factor is a predominantly unstructured peptide in DMSO. Similar results were obtained for the other peptides indicating that S-prenylation of Cys12 does not affect the conformation of these peptides.