C-terminal N-alkylated peptide amides resulting from the linker decomposition of the Rink amide resin a new cleavage mixture prevents their formation

Abstract:  C-terminal N-alkylated peptide amides resulting from the linker decomposition of the Rink amide resin: a new cleavage mixture prevents their formation. Stathopo ulos P, Papas S, Tsikaris V. Department of Chemistry, University of Ioannina, GR-45110 Ioannina, Greece. Decompositi on of the resin linkers during TFA cleavage of the peptides in the Fmoc strategy leads to alkylation of sensitive amino acids. The C-terminal amide alkylation, reported for the first time, is shown to be a major problem in peptide amides synthesized on the Rink amide resin. This side reaction occurs as a result of the Rink amide linker decomposition under TFA treatment of the peptide resin. The use of 1,3-dimethoxybenzene in a cleavage cocktail prevents almost quantitatively formation of C-terminal N-alkylated peptide amides. Oxidized by-product in the tested Cys- and Met-containing peptides were not observed, even if thiols were not used in the cleavage mixture. Copyright (c) 2005 European Peptide Society and John Wiley & Sons, Ltd. PMID: 16103992 [PubMed - indexed for MEDLINE]