A 1H STD NMR spectroscopic investigation of sialylnucleoside mimetics as probes of CMP-Kdn synthetase

Haselhorst, Thomas; Oschlies, Melanie; Abu-Izneid, Tareq; Kiefel, Milton J.; Tiralongo, Joe; Münster-Kühnel, Anja K.; Gerardy‐Schahn, Rita; Itzstein, Mark von

doi:10.1007/s10719-006-6735-y

Cited by 4 publications

(1 citation statement)

References 30 publications

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“…STD NMR has been applied as a method to assay for protein binding to libraries of potential targets ( , ) and, in investigations with aims similar to ours, as a means of mapping the binding epitope of a ligand at atomic resolution. The recognition characteristics of several carbohydrate- ( 22 , − , peptide- ( − ), and nucleotide-binding proteins () have been studied using STD NMR. STD signals arise as a result of through-space intermolecular magnetization transfer from selectively saturated resonances of a macromolecule to a bound ligand.…”

Section: Resultsmentioning

confidence: 99%

Recognition Characteristics of Monoclonal Antibodies That Are Cross-Reactive with Gangliosides and Lipooligosaccharide from Campylobacter jejuni Strains Associated with Guillain-Barré and Fisher Syndromes

et al. 2007

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The enteropathogen Campylobacter jejuni has the ability to synthesize glycan structures that are similar to mammalian gangliosides within the core component of its lipooligosaccharide (LOS). Exposure to ganglioside mimics in some individuals results in the production of autoantibodies that deleteriously attack nerve surface gangliosides, precipitating the onset of Guillain-Barré and Fisher syndromes (GBS and FS). We have characterized the interaction of four monoclonal antibodies (mAbs), established by sensitization of mice with LOS isolated from GBS- and FS-associated C. jejuni strains, with chemoenzymatically synthesized gangliooligosaccharides. Surface plasmon resonance (SPR) measurements demonstrate that three of the mAbs interact specifically with derivatives corresponding to their targeted gangliosides, with dissociation constants ranging from 10 to 20 microM. Antibody binding to the gangliooligosaccharides was probed by saturation transfer difference (STD) NMR spectroscopy. STD signals, resulting from antibody/oligosaccharide interaction, were observed for each of the four mAbs. In two cases, differential saturation transfer rates to oligosaccharide resonances enabled detailed epitope mapping. The binding of GD1a-S-Phe with GB1 is characterized by close association of the immunoglobulin with sites that are distributed over several residues of the oligosaccharide. This contrasts sharply with the profile observed for the binding of both GD3-S-Phe and GT1a-S-Phe with FS1. The close antigenic contacts in these ganglioside derivatives are confined to the N-acetylmannosaminyl portion of the terminal N-acetylneuraminic acid (NeuAc) residue of the disialosyl moiety. Our characterization of FS1 provides insight, at an atomic level, into how a single antigenic determinant presented by the LOS of C. jejuni can give rise to antibodies with binding promiscuity to [alphaNeuAc-(2-8)-alphaNeuAc]-bound epitopes and demonstrates why sera from FS patients have antibodies that are often reactive with more than one disialylated ganglioside.

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Section: Resultsmentioning

confidence: 99%

Recognition Characteristics of Monoclonal Antibodies That Are Cross-Reactive with Gangliosides and Lipooligosaccharide from Campylobacter jejuni Strains Associated with Guillain-Barré and Fisher Syndromes

et al. 2007

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Neisseria meningitidis Serogroup B Polysialyltransferase: Insights into Substrate Binding

et al. 2010

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On the loose: We report an STD NMR spectroscopic study of the polysialyltransferase from Neisseria meningitidis serogroup B (NmB‐polyST). The spectra reveal that the cytosine and ribose moiety receive more saturation than the sialic acid residue of CMP‐Neu5Ac. This loose binding enables a fast and efficient sialyl transfer to the acceptor substrate. Our analysis offers a view of the structural determinants necessary for binding to NmB‐polyST that provide the basis for the development of novel NmB‐polyST inhibitors.

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CMP‐Pseudaminic Acid is a Natural Potent Inhibitor of PseB, the First Enzyme of the Pseudaminic Acid Pathway in Campylobacter jejuni and Helicobacter pylori

McNally¹,

Schoenhofen²,

Houliston³

et al. 2008

ChemMedChem

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A 1H STD NMR spectroscopic investigation of sialylnucleoside mimetics as probes of CMP-Kdn synthetase

Cited by 4 publications

References 30 publications

Recognition Characteristics of Monoclonal Antibodies That Are Cross-Reactive with Gangliosides and Lipooligosaccharide from Campylobacter jejuni Strains Associated with Guillain-Barré and Fisher Syndromes

Recognition Characteristics of Monoclonal Antibodies That Are Cross-Reactive with Gangliosides and Lipooligosaccharide from Campylobacter jejuni Strains Associated with Guillain-Barré and Fisher Syndromes

Neisseria meningitidis Serogroup B Polysialyltransferase: Insights into Substrate Binding

CMP‐Pseudaminic Acid is a Natural Potent Inhibitor of PseB, the First Enzyme of the Pseudaminic Acid Pathway in Campylobacter jejuni and Helicobacter pylori

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