| Title: | Synthesis of S-alkyl and C-terminal analogs of the Saccharomyces cerevisiae a-factor. Influence of temperature on the stability of Fmoc and OFm groups toward HF |
| Author(s): | Xue CB; Becker JM; Naider F; |
| Address: | "Department of Chemistry, College of Staten Island, City University of New York" |
| DOI: | 10.1111/j.1399-3011.1991.tb00764.x |
| ISSN/ISBN: | 0367-8377 (Print) 0367-8377 (Linking) |
| Abstract: | "The a-mating factor of Saccharomyces cerevisiae Tyr-Ile-Ile-Lys-Gly-Val-Phe-Trp-Asp-Pro-Ala-Cys(farnesyl)OCH3, and 10 analogs modified at the cysteine side chain and/or the terminal carboxyl were synthesized using a combination of solid phase and solution phase methodologies. The strategy of synthesis involved the condensation of an amine terminal protected decapeptide with a carboxyl terminal S-alkylated dipeptide ester or amide using benzotriazol-l-yloxy-tris(methylamino)-phosphonium hexafluorophosphate as the coupling agent. The protected decapeptide was assembled on a PAM-resin using 9-fluorenylmethoxycarbonyl (Fmoc) for the protection of the Tyr alpha-amine and Lys epsilon-amine and 9-fluorenylmethyl ester (OFm) for the protection of the Asp beta-carboxyl. Premature loss of the OFm group from the HF cleavage was observed at 0-2 degrees, whereas no loss occurred when the cleavage reaction was conducted at -5 degrees. In contrast to these results, the OFm group in Asp(OFm) was partially removed by HF at -5 degrees and was completely stable to HF only at -20 degrees. The S-alkylated dipeptide esters were prepared, in yields from 64% to 88%, via thioalkylation of amine protected or unprotected dipeptide esters using potassium fluoride dihydrate as the base. The use of a tertiary amine as the base of thiohexadecanylation resulted in low reactivity" |
| Keywords: | "Alkylation Amino Acid Sequence Amino Acids Chromatography, High Pressure Liquid Dipeptides/chemical synthesis Fluorenes Mating Factor Molecular Sequence Data Peptides/*chemical synthesis/chemistry *Saccharomyces cerevisiae;" |
| Notes: | "MedlineXue, C B 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 1991/06/01 Int J Pept Protein Res. 1991 Jun; 37(6):476-86. doi: 10.1111/j.1399-3011.1991.tb00764.x" |
