Stabilization of Branched Oligosaccharides: Lewis x Benefits from a Nonconventional C−H···O Hydrogen Bond

Although animal lectins usually show a high degree of specificity for glycan structures, their single-site binding affinities are typically weak, a drawback which is often compensated in biological systems by an oligovalent presentation of carbohydrate epitopes. For the design of monovalent glycomimetics, structural information regarding solution and bound conformation of the carbohydrate lead represents a valuable starting point. In this paper, we focus on the conformation of the trisaccharide Lex (Gal[Fucα(1–3)]β(1–4)GlcNAc). Mainly because of the unfavorable tumbling regime, the elucidation of the solution conformation of Lex by NMR has only been partially successful so far. Lex was therefore attached to a 13C,15N-labeled protein. 13C,15N-filtered NOESY NMR techniques at ultrahigh field allowed increasing the maximal NOE enhancement, resulting in a high number of distance restraints per glycosidic bond and, consequently, a well-defined structure. In addition to the known contributors to the conformatio...