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Int J Pept Protein Res

Title:		Solution phase synthesis of Saccharomyces cerevisiae a-mating factor and its analogs
Author(s):		Xue CB; Ewenson A; Becker JM; Naider F;
Address:		"Department of Chemistry, College of Staten Island, City University of New York"
Journal Title:		Int J Pept Protein Res
Year:		1990
Volume:		36
Issue:		4
Page Number:		362 - 373
DOI:		10.1111/j.1399-3011.1990.tb01295.x
ISSN/ISBN:		0367-8377 (Print) 0367-8377 (Linking)
Abstract:		"The solution phase synthesis of the Saccharomyces cerevisiae a-mating factor and nonfarnesylated and nonmethylated a-factor analogs are reported. The a-factor, a lipopeptide with the sequence Tyr-Ile-Ile-Lys-Gly-Val-Phe-Trp-Asp-Pro-Ala-Cys(S-Farnesyl)OCH3 was synthesized by the condensation of the amine terminal protected decapeptide with the carboxyl terminal farnesylated dipeptide using benzotriazol-l-yloxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (BOP reagent) as the coupling agent. The synthesis of the decapeptide involved 5 + 5 fragment coupling with the BOP reagent and the successful application of 9-fluorenylmethyl ester(OFm) and 9-fluorenylmethoxycarbonyl(Fmoc) groups for the protection of Asp and Lys side chains and Tyr alpha-amine and of phenacyl esters (OPa) for alpha-carboxyl protection. The OFm and Fmoc groups tolerated repeated couplings and were completely stable to zinc powder in acetic acid, a condition under which the OPa group was removed. The synthesis of the nonfarnesylated alpha-factor was accomplished by the coupling of the decapeptide with tetrapeptide (Ala-CysOCH3)2 followed by the deprotection of the OFm and Fmoc groups with piperidine and the cleavage of the disulfide bond with zinc powder in acetic acid. The nonmethylated a-factor was prepared by 10 + 2 fragment coupling using OFm protection of the dipeptide carboxyl group followed by removal of all protecting groups with piperidine. Attempts to saponify a-factor were not successful. The synthetic nonfarnesylated and nonmethylated a-mating pheromones were 100-1000 times less active than the a-factor, indicating that although the methyl ester and the farnesyl group are not essential for biological activity, they are necessary for high potency"
Keywords:		"Amino Acid Sequence Chromatography, High Pressure Liquid Indicators and Reagents Magnetic Resonance Spectroscopy Mating Factor Molecular Sequence Data Optical Rotation Peptides/*chemical synthesis/isolation & purification/pharmacology Pheromones/*chemical;"
Notes:		"MedlineXue, C B Ewenson, A Becker, J M Naider, F eng GM22086/GM/NIGMS NIH HHS/ GM22087/GM/NIGMS NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Denmark 1990/10/01 Int J Pept Protein Res. 1990 Oct; 36(4):362-73. doi: 10.1111/j.1399-3011.1990.tb01295.x"