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Semi‐synthesis of a tag‐free O ‐GlcNAcylated tau protein by sequential chemoselective ligation
Author(s) -
Schwagerus Sergej,
Reimann Oliver,
Despres Clement,
SmetNocca Caroline,
Hackenberger Christian P. R.
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.2870
Subject(s) - native chemical ligation , peptide , moiety , ligation , chemical ligation , chemistry , phosphorylation , cysteine , biotin , combinatorial chemistry , biochemistry , stereochemistry , microbiology and biotechnology , biology , enzyme
In this paper, the first semi‐synthesis of the Alzheimer‐relevant tau protein carrying an O ‐GlcNAcylation is demonstrated by using sequential chemoselective ligation. The 52‐amino acid C‐terminus of tau was obtained by native chemical ligation between two synthetic peptide fragments, one carrying the O ‐GlcNAc moiety on Ser400, which has recently been demonstrated to inhibit tau phosphorylation and to hinder tau oligomerization, and the other equipped with a photocleavable biotin handle. After desulfurization to deliver a native alanine at the ligation junction, the N‐terminal cysteine was unmasked, and the peptide was further used for expressed protein ligation to generate the full‐length tau protein, which was purified by a photocleavable biotin tag. We thus provide a synthetic route to obtain a homogenous tag‐free O ‐GlcNAcylated tau protein that can further help to elucidate the significance of posttranslational modification on the tau protein and pave the way for evaluating possible drug targets in Alzheimer's disease. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.