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Article

Solvent Interactions and Conformational Choice in a Core N-Glycan Segment: Gas Phase Conformation of the Central, Branching Trimannose Unit and its Singly Hydrated Complex

Supporting Info

E. Cristina Stanca-Kaposta^†, David P. Gamblin^‡, Emilio J. Cocinero^†, Jann Frey^†, Romano T. Kroemer^#, Antony J. Fairbanks^‡, Benjamin G. Davis ^‡ and John P. Simons ^†

Department of Chemistry, University of Oxford, Physical and Theoretical Chemistry Laboratory, South Parks Road, OX1 3QZ Oxford, United Kingdom, Sanofi-Aventis, CRVA, 13 quai Jules Guesde, BP14, 94403 Vitry-sur-Seine, France, and the Department of Chemistry, University of Oxford, Chemistry Research Laboratory, 12 Mansfield Road, OX1 3TA Oxford, United Kingdom

J. Am. Chem. Soc., 2008, 130 (32), pp 10691–10696

DOI: 10.1021/ja801892h

Publication Date (Web): July 17, 2008

†

University of Oxford, Physical and Theoretical Chemistry Laboratory.

‡

University of Oxford, Chemistry Research Laboratory.

Sanofi-Aventis, CRVA.

Abstract

The intrinsic conformational preferences and structures of the branched trimannoside, α-phenyl 3,6-di-O-(α-d-mannopyranosyl)-α-d-mannopyranoside (which contains the same carbohydrates found in a key subunit of the core pentasaccharide in N-glycans) and its singly hydrated complex, have been investigated in the gas phase isolated at low temperature in a molecular beam expansion. Conformational assignments of their infrared ion dip spectra, based on comparisons between experiment and ONIOM (B3LYP/6-31+G(d):HF/6-31G(d)) and single-point MP2 calculations have identified their preferred structures and relative energies. The unhydrated trimannoside populates a unique structure supported by two strong, central hydrogen bonds linking the central mannose unit (CM), and its two branches (3M and 6M) closely together, through a cooperative hydrogen-bonding network: OH4(CM)→OH6(3M)→OH6(6M). A closely bound structure is also retained in the singly hydrated oligosaccharide, with the water molecule bridging across the 3M and 6M branches to provide additional bonding. This structure contrasts sharply with the more open, entropically favored trimannoside structure determined in aqueous solution at 298 K. In principle this structure can be accessed from the isolated trimannoside structure by a simple conformational change, a twist about the α(1,3) glycosidic linkage, increasing the dihedral angle ψ[C1(3M)−O3(3M)−C3(CM)−C2(CM)] from 74° to 146° to enable accommodation of a water molecule at the centrally bound site occupied by the hydroxymethyl group on the 3M ring and mediation of the water-linked hydrogen-bonded network: OH4(CM) →OH_W→OH6(6M). The creation of a “water pocket” motif localized at the bisecting axis of the trimannoside is strikingly similar to the structure of more complex N-glycans in water, suggesting perhaps a general role for the “bisecting” OH4 group in the central (CM) mannose unit.