| Title: | A superactive peptidomimetic analog of a farnesylated dodecapeptide yeast pheromone |
| Author(s): | Zhang YL; Dawe AL; Jiang Y; Becker JM; Naider F; |
| Address: | "Department of Chemistry, College of Staten Island, City University of New York, New York 10314, USA" |
| Journal Title: | Biochem Biophys Res Commun |
| ISSN/ISBN: | 0006-291X (Print) 0006-291X (Linking) |
| Abstract: | "The S. cerevisiae a-factor, YIIKGVFWDPAC(s-farnesyl)-OCH3, is one of two peptide mating pheromones which mediate cell-cell communication in S. cerevisiae. We previously reported that replacing Gly5 with D-Ala led to a 4-6 fold increase in activity while the L-Ala5 homolog was 4 to 16-fold less active than the wildtype. To clarify the structural implications of these findings, we conformationally restricted the center of the pheromone by inserting gamma-lactam constraints in place of either the Lys4Gly5 or the Gly5Val6 dipeptide unit. Incorporation of (R)-3-amino-2-oxo-1-pyrrolidineacetic acid in place of Lys4Gly5 led to a super-active agonist which exhibited a 32-fold higher bioactivity than that of the a-factor. In contrast, an analog with (S)-3-amino-2-oxo-1-pyrrolidineacetic acid in place of Gly5Val6 is about 30 to 60-fold less active than the a-factor. These data strongly suggest that the a-factor adopts a reverse turn as its bioactive conformation" |
| Keywords: | Amino Acid Sequence Indicators and Reagents Lactams Mating Factor Molecular Sequence Data Oligopeptides/*chemical synthesis/*pharmacology Peptides/*chemical synthesis/*pharmacology Pheromones/chemical synthesis/pharmacology Protein Prenylation Saccharomyc; |
| Notes: | "MedlineZhang, Y L Dawe, A L Jiang, Y Becker, J M Naider, F eng GM 22086/GM/NIGMS NIH HHS/ GM 22087/GM/NIGMS NIH HHS/ Comparative Study Research Support, U.S. Gov't, P.H.S. 1996/07/16 Biochem Biophys Res Commun. 1996 Jul 16; 224(2):327-31. doi: 10.1006/bbrc.1996.1028" |
