title: Semi-synthesis of a tag-free O-GlcNAcylated tau protein by sequential chemoselective ligation.
abstract: 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.
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie (FMP), Campus Berlin-Buch Robert-Roessle-Str. 10, 13125, Berlin, Germany.|Department Chemie, Humboldt Universität zu Berlin, Brook-Taylor-Strasse 2, 12489, Berlin, Germany.
authors.forename: Sergej
authors.initials: S
authors.lastname: Schwagerus
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie (FMP), Campus Berlin-Buch Robert-Roessle-Str. 10, 13125, Berlin, Germany.|Freie Universität Berlin, Institut für Chemie und Biochemie, Takustrasse 3, 14195, Berlin, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Reimann
authors.affiliation: UMR 8576 - UGSF, Univ. Lille, CNRS, Unité de Glycobiologie Structurale et Fonctionnelle, F-59000, Lille, France.|CNRS, UMR 8576, F-59000, Lille, France.
authors.forename: Clement
authors.initials: C
authors.lastname: Despres
authors.affiliation: UMR 8576 - UGSF, Univ. Lille, CNRS, Unité de Glycobiologie Structurale et Fonctionnelle, F-59000, Lille, France.|CNRS, UMR 8576, F-59000, Lille, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Smet-Nocca
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie (FMP), Campus Berlin-Buch Robert-Roessle-Str. 10, 13125, Berlin, Germany.|Department Chemie, Humboldt Universität zu Berlin, Brook-Taylor-Strasse 2, 12489, Berlin, Germany.
authors.forename: Christian P R
authors.initials: CP
authors.lastname: Hackenberger
mesh_terms: D000117:Acetylglucosamine / Q000737:chemistry*; D000544:Alzheimer Disease / Q000378:metabolism; D060326:Chemistry Techniques, Synthetic; D006801:Humans; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry; D011499:Protein Processing, Post-Translational; D012694:Serine / Q000737:chemistry*; D016875:tau Proteins / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D010455:Peptides; D016875:tau Proteins; D012694:Serine; D000117:Acetylglucosamine
keywords: O-GIcNac; native chemical ligation; protein synthesis; tag-free purification; tau protein