title: C-terminal N-alkylated peptide amides resulting from the linker decomposition of the Rink amide resin: a new cleavage mixture prevents their formation.
abstract: Decomposition 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.
authors.affiliation: Department of Chemistry, University of Ioannina, GR-45110 Ioannina, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Stathopoulos
authors.forename: Serafim
authors.initials: S
authors.lastname: Papas
authors.forename: Vassilios
authors.initials: V
authors.lastname: Tsikaris
mesh_terms: D000478:Alkylation; D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D000840:Anisoles / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003432:Cross-Linking Reagents / Q000737:chemistry; D005449:Fluorenes / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D012117:Resins, Synthetic / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D014269:Trifluoroacetic Acid / Q000737:chemistry*
chemical_list: D000577:Amides; D000840:Anisoles; D003432:Cross-Linking Reagents; D005449:Fluorenes; D010455:Peptides; D012117:Resins, Synthetic; C075825:Rink amide resin; C031201:1,3-dimethoxybenzene; D014269:Trifluoroacetic Acid