CONFORMATIONAL PHASE SPACE ANALYSIS OF LINKAGE-ISOMERS a-MANNOSE DISACCHARIDES BY HAMILTONIAN REPLICA EXCHANGE MD SIMULATIONS AND NMR EXPERIMENT

摘要

Mannose-containing oligosaccharides show the highest variability in terms of the types of inter-glycosidic linkage isomers between the individual sugar residues. This differentiation, together with the possibility for the mannose to be present in both the epimeric forms at the anomeric center, leads unequivocally to a complex net of conformational topologies which are associated with distinct biological roles. A range of mannose-containing biomolecules that cover these structural motifs are widely found in nature. Foremost amongst these structures are the N-glycans associated with immunity and infectious disease, particularly the mammalian high mannose-type N-linked glycan which plays an important role in the folding of glycoproteins in the endoplasmic reticulum[1]. Further mannose-containing forms can be found in the cell wall polysaccharides of Saccharomyces cerevisiae[2] and Mycobacterium smegmatis[3] or in glycosylphosphatidylinositol anchored glycoproteins.