Conformational changes of 1-4-glucopyranosyl residues of a sulfated CC linked hexasaccharide

Abstract This work describes the structure of a fully sulfated maltotriose alpha – beta C C linked dimer, where a central glycosidic bond was substituted by a non natural, hydrolase-resistant C C bond. Such compound shows anti-metastatic properties being an inhibitor of the heparanase enzymatic activity and of P-selectin-mediated cell–cell interactions. NMR spectroscopy was applied to investigate the structure and conformational properties of this C C linked hexasaccharide. The presence of sulfate substituents and the internal C C bond drives the two internal rings in an unusual 1 C 4 chair conformation, while the external rings linked by glycosidic bonds retain the typical 4 C 1 conformation. The NMR results were confirmed by molecular mechanics calculations using structure corresponding di- and tetrasaccharides as models.