| Title: | Synthesis of Peptides Containing C-Terminal Esters Using Trityl Side-Chain Anchoring: Applications to the Synthesis of C-Terminal Ester Analogs of the Saccharomyces cerevisiae Mating Pheromone a-Factor |
| Author(s): | Diaz-Rodriguez V; Ganusova E; Rappe TM; Becker JM; Distefano MD; |
| Address: | "Department of Microbiology, University of Tennessee , Knoxville, Tennessee 37996, United States" |
| ISSN/ISBN: | 1520-6904 (Electronic) 0022-3263 (Print) 0022-3263 (Linking) |
| Abstract: | "Peptides containing C-terminal esters are an important class of bioactive molecules that includes a-factor, a farnesylated dodecapeptide, involved in the mating of Saccharomyces cerevisiae. Here, results that expand the scope of solid-phase peptide synthetic methodology that uses trityl side-chain anchoring for the preparation of peptides with C-terminal cysteine alkyl esters are described. In this method, Fmoc-protected C-terminal cysteine esters are anchored to trityl chloride resin and extended by standard solid-phase procedures followed by acidolytic cleavage and HPLC purification. Analysis using a Gly-Phe-Cys-OMe model tripeptide revealed minimal epimerization of the C-terminal cysteine residue under basic conditions used for Fmoc deprotection. (1)H NMR analysis of the unfarnesylated a-factor precursor peptide confirmed the absence of epimerization. The side-chain anchoring method was used to produce wild-type a-factor that contains a C-terminal methyl ester along with ethyl-, isopropyl-, and benzyl-ester analogs in good yield. Activity assays using a yeast-mating assay demonstrate that while the ethyl and isopropyl esters manifest near-wild-type activity, the benzyl ester-containing analog is ca. 100-fold less active. This simple method opens the door to the synthesis of a variety of C-terminal ester-modified peptides that should be useful in studies of protein prenylation and other structurally related biological processes" |
| Keywords: | "Amino Acid Sequence Biological Phenomena Chromatography, High Pressure Liquid Cysteine/*chemistry Dipeptides/*chemistry Magnetic Resonance Spectroscopy Peptides/*chemical synthesis/chemistry Pheromones/*chemistry Saccharomyces cerevisiae/*chemistry Struct;" |
| Notes: | "MedlineDiaz-Rodriguez, Veronica Ganusova, Elena Rappe, Todd M Becker, Jeffrey M Distefano, Mark D eng 5T32GM008347-22/GM/NIGMS NIH HHS/ R01 GM058842/GM/NIGMS NIH HHS/ R01 GM022087/GM/NIGMS NIH HHS/ T32 GM008347/GM/NIGMS NIH HHS/ T32 GM008700/GM/NIGMS NIH HHS/ GM008700/GM/NIGMS NIH HHS/ GM058842/GM/NIGMS NIH HHS/ GM084152/GM/NIGMS NIH HHS/ R01 GM084152/GM/NIGMS NIH HHS/ GM22087/GM/NIGMS NIH HHS/ R56 GM022087/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural 2015/08/14 J Org Chem. 2015 Nov 20; 80(22):11266-74. doi: 10.1021/acs.joc.5b01376. Epub 2015 Aug 24" |
