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C ‐terminal N ‐alkylated peptide amides resulting from the linker decomposition of the Rink amide resin. A new cleavage mixture prevents their formation
Author(s) -
Stathopoulos Panagiotis,
Papas Serafim,
Tsikaris Vassilios
Publication year - 2006
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.706
Subject(s) - amide , chemistry , cleavage (geology) , alkylation , peptide , linker , decomposition , combinatorial chemistry , organic chemistry , stereochemistry , catalysis , biochemistry , materials science , fracture (geology) , computer science , composite material , operating system
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. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd.