CONFORMATIONAL-ANALYSIS OF ALPHA-D-FUC-(1-]4)-BETA-D-GLCNAC-OME - ONE-DIMENSIONAL TRANSIENT NOE EXPERIMENTS AND METROPOLIS MONTE-CARLO SIMULATIONS

One-dimensional transient NOE build-up curves were measured for the synthetic disaccharide alpha-D-Fuc-(1 --> 4)-beta-D-GlcNAc 1 utilizing Gaussian shaped pulses. Simulated build-up curves from Metropolis Monte Carlo simulations were compared to the experimental data. Disaccharide 1 is structurally related to methyl beta-D-maltoside in that it also contains an alpha-(1 --> 4) linkage, and it has the same configuration of groups around the glycosidic linkage. Analysis of NOEs in methyl beta-D-maltoside is restricted to those observed upon selective excitation of H1' because of severe spectral overlap. The situation is different in 1 where H-1-NMR signals are well separated. Several interglycosidic NOEs were observed. The corresponding build-up curves allowed an accurate determination of the conformational preferences at the glycosidic linkage in 1. Comparison of experimental and theoretical NOE build-up curves showed clearly that rigid minimum-energy models cannot account for the experimental data. The best fit of experimental NOE build-up curves was obtained with theoretical curves from a 2 x 10(6) step Metropolis Monte Carlo simulation with the temperature parameter set at 1000 K. Finally, it was observed that only the interglycosidic NOE H5'/H6-pro-S significantly depends upon varying conformation distributions at the alpha-(1 --> 4)-glycosidic linkage, induced by choosing different temperature parameters for the Metropolis Monte Carlo simulations.