title: Synthesis and molecular recognition studies of the HNK-1 trisaccharide and related oligosaccharides. The specificity of monoclonal anti-HNK-1 antibodies as assessed by surface plasmon resonance and STD NMR.
abstract: The human natural killer cell carbohydrate, HNK-1, plays function-conducive roles in peripheral nerve regeneration and synaptic plasticity. It is also the target of autoantibodies in polyneuropathies. It is thus important to synthesize structurally related HNK-1 carbohydrates for optimizing its function-conducive roles, and for diagnosis and neutralization of autoantibodies in the fatal Guillain-Barré syndrome. As a first step toward these goals, we have synthesized several HNK-1 carbohydrate derivatives to assess the specificity of monoclonal HNK-1 antibodies from rodents: 2-aminoethyl glycosides of selectively O-sulfated trisaccharide corresponding to the HNK-1 antigen, its nonsulfated analogue, and modified structures containing 3-O-fucosyl or 6-O-sulfo substituents in the N-acetylglucosamine residues. These were converted, together with several related oligosaccharides, into biotin-tagged probes to analyze the precise carbohydrate specificity of two anti-HNK-1 antibodies by surface plasmon resonance that revealed a crucial role of the glucuronic acid in antibody binding. The contribution of the different oligosaccharide moieties in the interaction was shown by saturation transfer difference (STD) NMR of the complex consisting of the HNK-1 pentasaccharide and the HNK-1 412 antibody.
authors.affiliation: Laboratory of Glycoconjugate Chemistry, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, 119991 Moscow, Russia.
authors.forename: Yury E
authors.initials: YE
authors.lastname: Tsvetkov
authors.forename: Monika
authors.initials: M
authors.lastname: Burg-Roderfeld
authors.forename: Gabriele
authors.initials: G
authors.lastname: Loers
authors.forename: Ana
authors.initials: A
authors.lastname: Ardá
authors.forename: Elena V
authors.initials: EV
authors.lastname: Sukhova
authors.forename: Elena A
authors.initials: EA
authors.lastname: Khatuntseva
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Grachev
authors.forename: Alexander O
authors.initials: AO
authors.lastname: Chizhov
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Siebert
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
authors.forename: Jesús
authors.initials: J
authors.lastname: Jiménez-Barbero
authors.forename: Nikolay E
authors.initials: NE
authors.lastname: Nifantiev
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D001710:Biotin / Q000378:metabolism; D018959:CD57 Antigens / Q000737:chemistry* / Q000276:immunology; D002240:Carbohydrate Sequence; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D020349:Surface Plasmon Resonance / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal; D018959:CD57 Antigens; D008024:Ligands; D009844:Oligosaccharides; D001710:Biotin