title: A PEGylated photocleavable auxiliary mediates the sequential enzymatic glycosylation and native chemical ligation of peptides.
abstract: Research aimed at understanding the specific role of glycosylation patterns in protein function would greatly benefit from additional approaches allowing direct access to homogeneous glycoproteins. Herein the development and application of an efficient approach for the synthesis of complex homogenously glycosylated peptides based on a multifunctional photocleavable auxiliary is described. The presence of a PEG polymer within the auxiliary enables sequential enzymatic glycosylation and straightforward isolation in excellent yields. The auxiliary-modified peptides can be directly used in native chemical ligations with peptide thioesters easily obtained by direct hydrazinolysis of the respective glycosylated peptidyl resins and subsequent oxidation. The ligated glycopeptides can be smoothly deprotected by UV irradiation. We apply this approach to the preparation of variants of the epithelial tumor marker MUC1 carrying one or more Tn, T, or sialyl-T antigens.
authors.affiliation: Fakultät Chemie, Institut für Biologische Chemie, Universität Wien, Währinger Strasse 38, 1090 Vienna (Austria).
authors.forename: Claudia
authors.initials: C
authors.lastname: Bello
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia, Athens (USA).
authors.forename: Shuo
authors.initials: S
authors.lastname: Wang
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia, Athens (USA).
authors.forename: Lu
authors.initials: L
authors.lastname: Meng
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia, Athens (USA).
authors.forename: Kelley W
authors.initials: KW
authors.lastname: Moremen
authors.affiliation: Fakultät Chemie, Institut für Biologische Chemie, Universität Wien, Währinger Strasse 38, 1090 Vienna (Austria). christian.becker@univie.ac.at.
authors.forename: Christian F W
authors.initials: CF
authors.lastname: Becker
mesh_terms: D006031:Glycosylation; D006801:Humans; D008026:Ligation; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis*; D046188:Protein Modification, Translational
chemical_list: D010455:Peptides
keywords: PEGylation; bioorganic chemistry; chemoenzymatic glycosylation; photocleavable ligation auxiliary; protein modifications