title: Biomimetic synthesis of the tumor-associated (2,3)-sialyl-T antigen and its incorporation into glycopeptide antigens from the mucins MUC1 and MUC4.
abstract: Glycoproteins on epithelial tumor cells often exhibit aberrant glycosylation profiles. The incomplete formation of the glycan side chains resulting from a down-regulated glucosamine transfer and a premature sialylation results in additional peptide epitopes, which become accessible to the immune system in mucin-type glycoproteins. These cancer-specific structure alterations are considered to be a promising basis for selective immunological attack on tumor cells. Among the tumor-associated saccharide antigens, the (2,3)-sialyl-T antigen has been identified as the most abundant glycan, found in several different carcinoma cell lines. According to a linear biomimetic strategy, the (2,3)-sialyl-T antigen was synthesized by a stepwise glycan chain extension of a protected galactosamine-threonine precursor. For the construction of immunostimulating antigens combining both peptide and saccharide motifs, this antigen was incorporated into glycopeptide partial structures from the mucins MUC1 and MUC4 by sequential solid-phase synthesis.
authors.affiliation: Institut für Organische Chemie der Universität Mainz, Duesbergweg 10-14, 55128 Mainz, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Dziadek
authors.forename: Constanze
authors.initials: C
authors.lastname: Brocke
authors.forename: Horst
authors.initials: H
authors.lastname: Kunz
mesh_terms: D000951:Antigens, Neoplasm / Q000737:chemistry*; D032701:Biomimetics; D019496:Cancer Vaccines / Q000138:chemical synthesis*; D002240:Carbohydrate Sequence; D002851:Chromatography, High Pressure Liquid; D006020:Glycopeptides / Q000138:chemical synthesis*; D006023:Glycoproteins / Q000138:chemical synthesis; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000737:chemistry*; D055264:Mucin-4; D009077:Mucins / Q000737:chemistry*; D020080:Tandem Repeat Sequences; D013912:Threonine / Q000737:chemistry
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D006020:Glycopeptides; D006023:Glycoproteins; D007202:Indicators and Reagents; D018396:Mucin-1; D055264:Mucin-4; D009077:Mucins; C505942:tumor-associated (2,3)-sialyl-T antigen; D013912:Threonine