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Removal of the 5‐nitro‐2‐pyridine‐sulfenyl protecting group from selenocysteine and cysteine by ascorbolysis
Author(s) -
Ste. Marie Emma J.,
Ruggles Erik L.,
Hondal Robert J.
Publication year - 2016
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.2908
Subject(s) - chemistry , thiolysis , selenocysteine , protecting group , cysteine , peptide , pyridine , electrophile , trifluoroacetic acid , thiol , combinatorial chemistry , covalent bond , leaving group , sulfanyl , medicinal chemistry , nitro , organic chemistry , biochemistry , antioxidant , catalysis , enzyme , polyphenol , alkyl , proanthocyanidin
We previously reported on a method for the facile removal of 4‐methoxybenzyl and acetamidomethyl protecting groups from cysteine (Cys) and selenocysteine (Sec) using 2,2′‐dithiobis‐5‐nitropyridine dissolved in trifluoroacetic acid, with or without thioanisole. The use of this reaction mixture removes the protecting group and replaces it with a 2‐thio(5‐nitropyridyl) (5‐Npys) group. This results in either a mixed selenosulfide bond or disulfide bond (depending on the use of Sec or Cys), which can subsequently be reduced by thiolysis. A major disadvantage of thiolysis is that excess thiol must be used to drive the reaction to completion and then removed before using the Cys‐containing or Sec‐containing peptide in further applications. Here, we report a further advancement of this method as we have found that ascorbate at pH 4.5 and 25 °C will reduce the selenosulfide to the selenol. Ascorbolysis of the mixed disulfide between Cys and 5‐Npys is much less efficient but can be accomplished at higher concentrations of ascorbate at pH 7 and 37 °C with extended reaction times. We envision that our improved method will allow for in situ reactions with alkylating agents and electrophiles without the need for further purification, as well as a number of other applications. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.