Conformational studies of carbohydrates: MD simulation and NMR spectroscopy

Sammanfattning: This thesis describes various aspects of conformational studies of carbohydrates, from development of the methods by which experimental parameters are gathered to the application of NMR spectroscopy and MD simulation for the analysis of a disaccharide. Paper I describes the use of site-specific 13C labeling as a tool to resolve spectral overlap of 1H frequencies in a trisaccharide, allowing the measurement of important crossrelaxation rates and long-range couplings which were previously obscured. The newly acquired parameters are found to support the conformational equilibrium proposed in a previous study of the molecule. Paper II describes a problem in the J-HMBC experiment that occurs when there are large homonuclear 13C scalar couplings present, a situation typically occurring when studying labeled compounds. By introducing a constant-time element to the pulse-program, the interference by one-bond homonuclear 1JC,C couplings is shown to be suppressed when applied to site-specifically labeled disaccharides. The last project, paper III, concerns the conformation and dynamics of the disaccharide β-L-Fucp-(1→6)-α-D-Glcp-OMe, showing the difficulties associated with the flexible nature of (1→6) linkages. The molecule is found to have significant flexiblity in both the ω and ψ torsions. A three-state equilibrium is found for ω, while ψ has two states connected by a low barrier. The force field parm22/SU01 is able to reproduce and explain the experimental parameters reasonably well, but it is concluded that some of the states have slightly incorrect torsion angles and that the populations are not correctly represented.