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An important side reaction using the thiol, 3,6‐dioxa‐1,8‐octanedithiol (DODT), in 9‐fluorenylmethoxycarbonyl‐based solid phase peptide synthesis
Author(s) -
Harris Paul W. R.,
Kowalczyk Renata,
Yang SungHyun,
Williams Geoffrey M.,
Brimble Margaret A.
Publication year - 2014
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.2595
Subject(s) - thioether , chemistry , peptide , methionine sulfoxide , peptide synthesis , alkylation , methionine , sulfoxide , thiol , aqueous solution , solid phase synthesis , dimethyl sulfoxide , combinatorial chemistry , amino acid , mass spectrometry , cleavage (geology) , dithiol , organic chemistry , chromatography , catalysis , biochemistry , geotechnical engineering , fracture (geology) , engineering
A considerable quantity of an alkylation by‐product is observed when using 3,6‐dioxa‐1,8‐octanedithiol as a scavenger during acidic release of peptides containing the thioether amino acid methionine from the solid support. Adjustment of the cleavage conditions by replacement of 3,6‐dioxa‐1,8‐octanedithiol with ethane dithiol or by using methionine sulfoxide as an alternative to methionine resulted in no such impurity. The by‐product was detectable by liquid chromatography and mass spectrometry and characterised by NMR spectroscopy of an isolated model peptide. It could be effectively removed in a separate post cleavage step by treatment with dilute aqueous acid at 37 °C. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.