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.
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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. / Tsvetkov, Yury E; Burg-Roderfeld, Monika; Loers, Gabriele; Ardá, Ana; Sukhova, Elena V; Khatuntseva, Elena A; Grachev, Alexey A; Chizhov, Alexander O; Siebert, Hans-Christian; Schachner, Melitta; Jiménez-Barbero, Jesús; Nifantiev, Nikolay E.
in: J AM CHEM SOC, Jahrgang 134, Nr. 1, 1, 2012, S. 426-435.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - 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.
AU - Tsvetkov, Yury E
AU - Burg-Roderfeld, Monika
AU - Loers, Gabriele
AU - Ardá, Ana
AU - Sukhova, Elena V
AU - Khatuntseva, Elena A
AU - Grachev, Alexey A
AU - Chizhov, Alexander O
AU - Siebert, Hans-Christian
AU - Schachner, Melitta
AU - Jiménez-Barbero, Jesús
AU - Nifantiev, Nikolay E
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Ligands
KW - Molecular Sequence Data
KW - Carbohydrate Sequence
KW - Magnetic Resonance Spectroscopy/methods
KW - Antibodies, Monoclonal/immunology
KW - Antibody Specificity
KW - Antigens, CD57/chemistry/immunology
KW - Biotin/metabolism
KW - Oligosaccharides/chemical synthesis/chemistry/immunology/metabolism
KW - Surface Plasmon Resonance/methods
KW - Ligands
KW - Molecular Sequence Data
KW - Carbohydrate Sequence
KW - Magnetic Resonance Spectroscopy/methods
KW - Antibodies, Monoclonal/immunology
KW - Antibody Specificity
KW - Antigens, CD57/chemistry/immunology
KW - Biotin/metabolism
KW - Oligosaccharides/chemical synthesis/chemistry/immunology/metabolism
KW - Surface Plasmon Resonance/methods
M3 - SCORING: Journal article
VL - 134
SP - 426
EP - 435
JO - J AM CHEM SOC
JF - J AM CHEM SOC
SN - 0002-7863
IS - 1
M1 - 1
ER -
