Rapid Communication investigation of oligosaccharide conformation using NMR dipolar couplings in an aqueous dilute liquid crystalline medium

ABSTRACT : The tetrasaccharide lacto-N-neotetraose Glcp was dissolved in a dilute mixture of dimyristoyl-and dihexanoylphosphatidylcholine in deuterium oxide and 1J(C,H) spinÈspin coupling constants were measured in an isotropic solution at 25 ¡C. On raising the temperature to 38 ¡C, an ordering of the system occurs which permits determination of dipolar couplings. An energy minimized molecular mechanics model was generated showing that the molecule is anisotropic and can be treated as a cylinder. A Ðt of the expression for the carbonÈproton dipolar couplings in a uniaxial molecule in a uniaxial liquid crystal revealed good agreement with experimental data, emphasizing the future potential of the method in studies of carbohydrate conformation

Solution structure of Mannobioses unravelled by means of Raman optical activity

Structural analysis of carbohydrates is a complicated endeavour, due to the complexity and diversity of the samples at hand. Herein, we apply a combined computational and experimental approach, employing molecular dynamics (MD) and density functional theory (DFT) calculations together with NMR and Raman optical activity (ROA) measurements, in the structural study of three mannobiose disaccharides, consisting of two mannoses with varying glycosidic linkages. The disaccharide structures make up the scaffold of high mannose glycans and are therefore important targets for structural analysis. Based on the MD population analysis and NMR, the major conformers of each mannobiose were identified and used as input for DFT analysis. By systematically varying the solvent models used to describe water interacting with the molecules and applying overlap integral analysis to the resulting calculational ROA spectra, we found that a full quantum mechanical/molecular mechanical approach is required for an optimal calculation of the ROA parameters. Subsequent normal mode analysis of the predicted vibrational modes was attempted in order to identify possible marker bands for glycosidic linkages. However, the normal mode vibrations of the mannobioses are completely delocalised, presumably due to conformational flexibility in these compounds, rendering the identification of isolated marker bands unfeasible

NMR and molecular modeling studies of the interaction between wheat germ agglutinin and the β-D-GlcpNAc-(1→6)-α-D-Manp epitope present in glycoproteins of tumor cells

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Conformation of the glycosidic linkage in a disaccharide investigated by double-quantum solid-state NMR

Double-quantum heteronuclear local field NMR is performed on a sample of a 13C2-labeled disaccharide, in which the two 13C spins are located on opposite sides of the glycosidic linkage. The evolution of the double-quantum coherences is found to be consistent with the solid-state conformation of the molecule, as previously determined by X-ray diffraction. The dependence of the double-quantum evolution on the glycosidic torsional angles is examined by using a graphical molecular manipulation program interfaced to a numerical spin simulation module