Synthesis of biologically active analogs of the dodecapeptide a-factor mating pheromone of Saccharomyces cerevisiae.
A number of dodecapeptides with the sequence YIIKGVFWDPAC were synthesized using solid phase peptide synthesis. The purity of the crude cleavage product was found to be directly related to the cysteine protecting group and the conditions employed for cleavage of the peptide from the resin. When 4-methyl-benzyl cysteine was used, complete deprotection was only achieved with low-high HF conditions at temperatures of 10 degrees-25 degrees, whereas milder conditions could be used for dodecapeptides containing ethyl cysteine or acetamidomethyl cysteine. In several syntheses the biological activity of the crude cleavage product greatly exceeded the biological activity of a purified major peptide component. The high activity found in the crude cleavage peptide was probably due to minor peptide side products in which the cysteine sulfur was alkylated by hydrophobic species during HF treatment. Two dodecapeptides, YIIKGVFWDPAC and YIIKGFWDPAC(Ethyl), had significant a-factor activity against MAT alpha strains of Saccharomyces cerevisiae. These peptides represent the first synthetic analogs with a-factor activity.
Ewenson
A
A
Department of Chemistry, College of Staten Island, City University of New York.
Marcus
S
S
Becker
J M
JM
Naider
F
F
D000595:Amino Acid Sequence; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003545:Cysteine; D006858:Hydrofluoric Acid; D000072235:Mating Factor; D008698:Mesylates; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D010455:Peptides / Q000138:chemical synthesis*; D010675:Pheromones; D012441:Saccharomyces cerevisiae / Q000032:analysis* / Q000187:drug effects / Q000254:growth & development; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds
D008698:Mesylates; D009842:Oligopeptides; D010455:Peptides; D010675:Pheromones; D013438:Sulfhydryl Compounds; D000072235:Mating Factor; C012077:trifluoromethanesulfonic acid; D003545:Cysteine; D006858:Hydrofluoric Acid