Synthesis and O-Glycosidic Linkage Conformational Analysis of C-13-Labeled Oligosaccharide Fragments of an Antifreeze Glycolipid

摘要

NMR studies of two C-13-labeled disaccharides and a tetrasaccharide were undertaken that comprise the backbone of a novel thermal hysteresis glycolipid containing a linear glycan sequence of alternating [beta Xylp-(1 -> 4)-beta Manp-(1 -> 4)](n) dimers. Experimental trans-glycoside NMR J-couplings, parameterized equations obtained from density functional theory (DFT) calculations, and an in-house circular statistics package (MA'AT) were used to derive conformational models of linkage torsion angles phi and psi in solution, which were compared to those obtained from molecular dynamics simulations. Modeling using different probability distribution functions showed that MA'AT models of phi in beta Man(1 -> 4)beta Xyl and beta Xyl(1 -> 4)beta Man linkages are very similar in the disaccharide building blocks, whereas MA'AT models of psi differ. This pattern is conserved in the tetrasaccharide, showing that linkage context does not influence linkage geometry in this linear system. Good agreement was observed between the MA'AT and MD models of psi with respect to mean values and circular standard deviations. Significant differences were observed for phi, indicating that revision of the force-field employed by GLYCAM is probably needed. Incorporation of the experimental models of phi and psi into the backbone of an octasaccharide fragment leads to a helical amphipathic topography that may affect the thermal hysteresis properties of the glycolipid.