Direct Evidence for Hydrogen Bonding in Glycans: A Combined NMR and Molecular Dynamics Study

Abstract

We introduce the abundant hydroxyl groups of glycans as NMR handles and structural probes to expand the repertoire of tools for structure–function studies on glycans in solution. To this end, we present the facile detection and assignment of hydroxyl groups in a wide range of sample concentrations (0.5–1700 mM) and temperatures, ranging from −5 to 25 °C. We then exploit this information to directly detect hydrogen bonds, well-known for their importance in molecular structural determination through NMR. Via HSQC-TOCSY, we were able to determine the directionality of these hydrogen bonds in sucrose. Furthermore, by means of molecular dynamics simulations in conjunction with NMR, we establish that one out of the three detected hydrogen bonds arises from intermolecular interactions. This finding may shed light on glycan–glycan interactions and glycan recognition by proteins