On the flexibility of the Lewis x, Lewis a, sialyl Lewis x, and sialyl Lewis a oligosaccharides - Conformational analysis in-solution by molecular modelling

The three-dimensional structure and conformational behaviour of the disaccharide alpha-D-Neu5Ac-(2-->3)-beta-D-Gal (I), two trisaccharides beta-D-Gal-(1-->3)-[alpha-L-Fuc-(1-->4)]-beta-D-GlcNAc (Lewis a, II) and beta-D-Gal-(1-->4)-[alpha-L-Fuc-(1-->3)]-beta-D-GlcNAc (Lewis x, III), and two tetrasaccharides alpha-D-Neu5Ac-(2-->3)-beta-D-Gal-(1-->3)-[alpha-L-Fuc-(1-->4)]-beta-D-GlcNAc (sialyl Lewis a, IV) and alpha-D-Neu5Ac-(2-->3)-beta-D-Gal-(1-->4)- [alpha-L-Fuc-(1-->3)]-beta-D-GlcNAc (sialyl Lewis x, V) in solution have been established using molecular modelling methods. The conformations available for each tri- and tetrasaccharide have been based on the minima available for disaccharide constituents of these oligosaccharides. The structure of the minima was calculated by molecular mechanics program RAMM which uses the MM2 force field in conjunction with the Monte Carlo simulation for a determination of the best side group orientations and with the evaluation of solvent effects, Abundances of conformers appear to depend strongly on the solvent. Comparison showed that calculated average vicinal carbon-proton coupling constants [(3)J(C,H)] are in good agreement with available experimental data. These results imply that the flexibility of these compounds is larger than assumed up to now.