Ab initio conformational study of two Lewis X analogues

This paper presents the first ab initio conformational study for analogues of a histo-blood group carbohydrate antigen, Le(x) (Gal-beta-1,4-[Fuc-alpha -1,3]-GlcNAc). In these analogues, the GlcNAc group of Le(x) was replaced b y a cyclohexanediol or an ethanediol group. The lowest energy conformers of these molecules were first found by the MM2*-SUMM conformational search te chnique. The molecular geometries and energies of lowest energy rotamers (w ithin a 3 kcal/mol energy window) were further analyzed at the HF/6-31G(d) level of theory. This study provides a detailed description of the hydrogen -bonding properties of the low-energy conformers yielded by the MM2* and ab initio methods. The key torsion angles for Fuc-alpha-1,3-GlcNAc and Gal-be ta-1,4-GlcNAc glycosidic bonds in Le(x) mostly keep their value in the diff erent environments (solid, liquid, and gas phase). The ab initio torsion an gles agree considerably better with the experimental results than the MM2* results. Another essential difference between the MM2* and ab initio result s is that the latter provide better differentiation of the rotamers. Comple xes with selectins introduced varying levels of distortion of Le(x), with t he most tightly bound structure being most distorted. Nonstacked rotamers o ccur only once among the rotamers of 1,2-cyclohexanediol analogue, and that rotamer is not particularly stable (Delta E = 2.3 kcal/mol). However, such kind of rotamers are more frequent among the rotamers of 1,2-ethanediol an alogue. This clearly shows that while the conformational space of 1,2-cyclo hexanediol analogue is rather similar to that of Le(x), the conformational space of 1,2-ethanediol analogue is considerably less similar.