CONFORMATIONAL-ANALYSIS OF DISACCHARIDE FRAGMENTS OF BLOOD-GROUP DETERMINANTS IN SOLUTION BY MOLECULAR MODELING

A detailed investigation has been undertaken on the conformational beh aviour of seven disaccharide fragments from blood group determinants o f 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 ener gy 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 dete rmination 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 approac h showed a very restricted motion about glycosidic linkages, the relax ed maps implied considerable increase of flexibility and several confo rmers were found for each of glycosidic linkages. Abundances of confor mers appear to depend on the solvent. Comparison shows that the calcul ated data are in agreement with the available experimental data.