Conformational changes of 1-4-glucopyranosyl residues of a sulfated C[sbnd]C linked hexasaccharide

Abstract

This work describes the structure of a fully sulfated maltotriose alpha–beta CC linked dimer, where a central glycosidic bond was substituted by a non natural, hydrolase-resistant CC 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 CC linked hexasaccharide. The presence of sulfate substituents and the internal CC bond drives the two internal rings in an unusual 1C4 chair conformation, while the external rings linked by glycosidic bonds retain the typical 4C1 conformation. The NMR results were confirmed by molecular mechanics calculations using structure corresponding di- and tetrasaccharides as models.