CONFORMATIONAL-CHANGES DUE TO VICINAL GLYCOSYLATION - THE BRANCHED LPHA-L-RHAP(1-2)[BETA-D-GALP(1-3)]-BETA-D-GLC1-OME TRISACCHARIDE COMPARED WITH ITS PARENT DISACCHARIDES

Conformations of the alpha-L-Rhap(1-2)-beta-D-Glc1-OMe and beta-D-Galp (1-3)-beta-D-Glc1-OMe disaccharides and the branched title trisacchari de were examined in DMSO-d(6) solution by H-1-nmr. The distance mappin g procedure was based on rotating frame nuclear Overhauser effect (NOE ) constraints involving C- and O-linked protons, and hydrogen-bond con straints manifested by the splitting of the OH nmr signals for partial ly deuteriated samples An ''isotopomer-selected NOE'' method for the u nequivocal identification of mutually hydrogen-bonded hydroxyl groups was suggested. The length of hydrogen bonds thus detected is considere d the only one motionally nonaveraged nmr-derived constraint. Molecula r mechanics and molecular dynamics methods were used to model the conf ormational properties of the studied oligosaccharides. Complex conform ational search, relying on a regular Phi,Psi-grid based scanning of th e conformational space of the selected glycosidic linkage combined wit h simultaneous modeling of different allowed orientations of the penda nt groups and the third, neighboring sugar residue, has been carried o ut. Energy minimizations were performed for each member of the Phi,Psi grid generated set of conformations. Conformational clustering has be en done to group the minimized conformations into families with simila r values of glycosidic torsion angles. Several stable syn and anti con formations were found for the 1-->2 and 1-->3 bonds in the studied dis accharides. Vicinal glycosylation affected strongly the occupancy of c onformational states in both branches of the title trisaccharide. The preferred conformational family of the trisaccharide (with average Phi ,Psi values of 38 degrees, 17 degrees for the 1-->2 and 48 degrees 1 d egrees for the 1-->3 bond respectively) was shown by nmr to be stabili zed by intramolecular hydrogen bonding between the nonbonded Rha and G al residues (C) 1998 John Wiley & Sons, Inc.