Conformational analysis of disaccharide fragments of blood group determinants in solution by molecular modelling

A detailed investigation has been undertaken on the conformational behaviour of seven disaccharide fragments from blood group determinants of Type 1 and Type 2, namely beta-D-Gal-(1-->3)-beta-D-GlcNAc (I), beta-D-Gal-(1-->4)-beta-D-GlcNAc (II), alpha-L-Fuc-(1-->2)-beta-D-Gal (III), alpha-L-Fuc-(1-->3)-beta-D-GlcNAc (IV), alpha-L-Fuc-(1-->4)-beta-D-GlcNAc (V), alpha-D-Gal-(1-->3)-beta-D-Gal (VI), and alpha-D-GalNAc-(1-->3)-beta-D-Gal (VII) in solution using molecular modelling methods. Two-dimensional rigid and adiabatic (Phi,Psi) maps describing the energy as a function of rotation around corresponding glycosidic Linkages were calculated by the RAMM molecular mechanics program which uses MM2(87) force field in conjunction with Monte Carlo simulation for a determination of the best side group orientations and with the evaluation of solvation effects. This approach predicted different conformational behaviour exhibited by these disaccharides. Whereas the rigid approach showed a very restricted motion about glycosidic linkages, the relaxed maps implied considerable increase of flexibility and several conformers were found for each of glycosidic linkages. Abundances of conformers appear to depend on the solvent. Comparison shows that the calculated data are in agreement with the available experimental data.