Conformational changes of 1-4-glucopyranosyl residues of a sulfated C-C 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.

Keywords: (1)C(4) chair conformation; Maltotriose; Molecular mechanics; NOESY spectroscopy; Sulfated CC oligosaccharides; Sulfated oligosaccharide-based drugs.