Conformational studies of the two anomeric methyl glycosides of α-D-Manp-(1→2)-D-Glcp by molecular simulations and NMR1H,1H T-ROESY experiments

Abstract

A conformational study has been performed of the two disaccharides α-D-Manp-(1→2)-α-D-Glcp-OMe (1) and α-D-Manp-(1→2)-β-D-Glcp-OMe (2) differing only in the anomeric configuration at the methyl glucoside. Molecular simulations were carried out with five different potential energy functions ranging from pure in vacuo to explicit solvent treatment. For comparison, ¹H,¹H T-ROESY and heteronuclear trans-glycosidic correlation NMR experiments were performed which resulted in proton–proton distances and ³J_C,H values, respectively. In addition, interpretation of ¹³C NMR glycosylation shifts indicated slightly different average conformations of the two disaccharides. From the molecular simulations selected parameters were calculated for comparison to experiments. The combined analysis revealed the conformational region of the disaccharides and showed that the average ψ torsion angle in 2 was more eclipsed than in 1. Moreover, the translational diffusion coefficients of the disaccharides were determined at 25 °C in D₂O by the Longitudinal Eddy-Delayed experiment which resulted in D_t = 0.37 × 10⁻⁹ m² s⁻¹. These values were compared to those obtained from molecular dynamics simulations with explicit water as solvent. The relative differences in translational diffusion between the disaccharides and water were similar for experiment and simulation. However, it is well-known that the TIP3P water model overestimates D_t, so also in these simulations.