Studies on the yeast alpha-mating factor: a model for mammalian peptide hormones

Small peptides initiate sexual conjugation in the yeast Saccharomyces cerevisiae and this phenomenon is an ideal paradigm for studying the mode of action of mammalian peptide hormones. 1H-nmr spectroscopy was used to examine the conformation of linear and cyclic analogues of the alpha-factor (WHWLQLKPGQPMY) in aqueous solution. In all cases peptides that exhibit nmr parameters expected for a type II beta-turn have higher biological activities than those that do not appear to assume this conformation. Based on a simple model for the interaction of the pheromone with its receptor, we prepared fragments of the alpha-factor. Several of these fragments either antagonize or potentiate the activity of the alpha-factor. The latter represent the first example of peptide fragments that synergize the activity of the parent pheromone.