The conformational behavior of tumor-associated carbohydrate antigens (TACAs) dimLe(x) and Le(a)Le(x) was studied using a combination of NMR experiments and molecular dynamics simulations. It is shown that within the hexasaccharides, the Le(x) and Le(a) branched trisaccharide fragments adopt the rigid "stacked" conformation known for the isolated trisaccharide antigens. In contrast, the β-D-GlcNAc-(1→3)-D-Gal glycosidic bond that connects the two Le(x) trisaccharides in dimLe(x), and the Le(a) trisaccharide to the Le(x) trisaccharide in Le(a)Le(x), was found to be very flexible in both hexasaccharides. Our results show that two distinct conformations, differing by the value of the Ψ angle for this glycosidic bond, are populated in solution. While the relative proportions of the two conformations in solution could not be determined accurately, experimental measurements indicate that both conformations are populated in significant amounts.
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