title: Synthesis of a glycopeptide vaccine conjugate for induction of antibodies recognizing O-mannosyl glycopeptides.
abstract: In spite of the clear importance of protein O-mannosylation in brain glycobiology, tools are lacking for specific detection, enrichment, and identification of proteins containing these modifycations. We envisioned inducing antibodies that specifically recognize O-mannose glycans on proteins and peptides. With this in mind, we prepared a glycopeptide vaccine construct containing the N-acetyllactosamine-extended mannose motif Galβ1-4GlcNAcβ1-2ManαThr, found as a common core structure on almost all mammalian O-mannosyl glycoproteins identified. O-mannose glycosylated amino acid building blocks and the corresponding glycopeptides were prepared by chemical synthesis and then conjugated to an immune carrier protein. After administration of the synthetic vaccine into rabbits, strong immune responses were obtained. Further evaluation by ELISA neutralization experiments and glycopeptide microarrays showed that the induced antibodies were highly specific to the glycopeptide antigen.
authors.affiliation: Gesellschaft zur Förderung der Analytischen Wissenschaften e.V. ISAS-Leibniz Institute for Analytical Sciences, Otto-Hahn-Str. 6b, 44227 Dortmund (Germany).
authors.forename: Jin
authors.initials: J
authors.lastname: Yu
authors.forename: Ulrika
authors.initials: U
authors.lastname: Westerlind
mesh_terms: D000606:Amino Sugars / Q000737:chemistry; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000917:Antibody Formation; D002240:Carbohydrate Sequence; D002417:Cattle; D004797:Enzyme-Linked Immunosorbent Assay; D006020:Glycopeptides / Q000737:chemistry / Q000276:immunology*; D006031:Glycosylation; D008358:Mannose / Q000737:chemistry*; D008969:Molecular Sequence Data; D011817:Rabbits; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000276:immunology; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000276:immunology*
chemical_list: D000606:Amino Sugars; D000906:Antibodies; D006020:Glycopeptides; D014614:Vaccines, Synthetic; D012710:Serum Albumin, Bovine; C000458:N-acetyllactosamine; D008358:Mannose
keywords: antibodies; carbohydrates; glycopeptides; glycosylation; vaccines