The conformation of glycans of the oligo-D-mannosidic type, and their interaction with concanavalin A: a...

The favored conformations of glycans of the oligo-D-mannosidic type have been determined by using empirical energy calculations. An interesting aspect is that the alpha-(1----3)-linked terminal D-mannose residue of the outer trimannosidic core fragment, in all the conformations which fall within 5 kcal.mol-1 of the global minimum, always lies close to the chitobiose core. These models are in general agreement with the available n.m.r. data. The probable modes of binding of these glycans to concanavalin A (Con A) were determined, by using a computer-modelling technique which identifies the positions for the different conformers of the carbohydrate in the binding site of Con A, based on stereochemical considerations. These studies showed that Con A can bind only to two of the three terminal D-mannose residues in these glycans, because the D-mannose residue which lies close to the chitobiose core is inaccessible for the binding of Con A. Of these two terminal D-mannose residues, the alpha-(1----6)-linked D-mannose may bind the more strongly. Furthermore, it is shown that the internal D-mannose residue will, at best, interact very weakly with the carbohydrate-binding site of Con A. These results rationalize well the available data on the binding affinity of these glycans to Con A. They further support the conclusion that the binding affinity of a glycan to Con A does not depend on the number in the glycan, of D-mannose residues which possess free 3-, 4-, and 6-hydroxyl groups, but, rather, on the accessibility of these residues to Con A.