NMR characterization and molecular modeling of fucoidan showing the importance of oligosaccharide branching in its anticomplementary activity.
Fucoidan is a potent inhibitor of the human complement system whose activity is mediated through interactions with certain proteins belonging to the classical pathway, particularly the protein C4. Branched fucoidan oligosaccharides displayed a higher anticomplementary activity as compared to linear structures. Nuclear magnetic resonance (NMR) characterization of the branched oligosaccharides and saturation transfer difference-NMR experiment of the interaction with the protein C4 allowed the identification of the glycan residues in close contact with the target protein. Transferred nuclear Overhauser effect spectroscopy experiment and molecular modeling of fucoidan oligosaccharides indicated that the presence of side chains reduces the flexibility of the oligosaccharide backbone, which thus adopts a conformation which is very close to the one recognized by the protein C4. Together, these results suggest that branching of fucoidan oligosaccharides, determining their conformational state, has a major impact on their anticomplementary activity.
Clément
Marie-Jeanne
MJ
CNRS UMR 8587, Laboratoire Analyse et Environnement, Université d'Evry Val d'Essonne, rue du Père Jarlan, 91025 Evry Cedex, France.
Tissot
Bérangère
B
Chevolot
Lionel
L
Adjadj
Elisabeth
E
Du
Yuguo
Y
Curmi
Patrick A
PA
Daniel
Régis
R
D002240:Carbohydrate Sequence; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry*; D011134:Polysaccharides / Q000737:chemistry*
D009844:Oligosaccharides; D011134:Polysaccharides; C007789:fucoidan