A conformational study of alpha-D-Manp-(1->2)-alpha-D-Manp-(1->OMICRON)-L-Ser by NMR ~1H,~1H T-ROESY experiments and molecular-dynamics simulations

摘要

The conformational preference of alpha-D-Manp-(1->2)-alpha-D-Manp-(1->OMICRON)-L-Ser has been investigated by one-dimensional ~1H,~1H T-ROESY experiments and molecular-dynamics simulations with CHARMM22 type of force fields and water as explicit solvent.Proton-proton distances were obtained from the simulations and subsequently experimentally determiend distances couldbe derived.measurements were performed on the title compound as well as on selectively deuterium-substtuted analogues synthesized as part of this study to alleviate possible NMR spectroscopic difficulties.A very goodjagreement was present between the separate NMR experiments.In the subsequent analysis a key nuclear Overhauser effect between theanomieric protons in the two sugar residues wasused ot assess the conformational dynamics revealed by the molecular simulations.The combined results support a model in which two states are significantly populated as a result of flexibility around the bond defined by the glycosidic torsion angle PSI.