Theoretical studies on the modes of binding of some of the derivatives of D-mannose to concanavalin A

Abstract

The possible modes of binding for methyl-α -D-mannopyranoside, methyl-β -D-mannopyranoside, 2-O-methyl-α -D-mannopyranoside, methyl-2-O-methyl-α -D-mannopyranoside and methyl-α -D-N-acetylmannosamine to concanavalin A have been investigated using theoretical methods. All these sugars, except methyl-α -D-N-acetylmannosamine, reach the active site of concanavalin A with a highly restricted number of binding orientations. Present investigations suggest that the failure of methyl-α -D-N-acetylmannosamine to bind to concanavalin A is not so much due to steric factors as to repulsive electrostatic interactions. Methyl-2-O-methyl-α -D-mannopyranoside can bind to concanavalin A in one mode whereas the other sugars can bind in more than one mode. The high potency of methyl-α -D-mannopyranoside over methyl-β -D-mannopyranoside is mainly due to the possibility of hydrophobic interactions of the a-methoxy group with Leu(99) or Tyr(100) and also due to the possibility of formation of better and more hydrogen bonds with the protein. A comparison of these data with those for the d-glucopyranosides suggests that the change of the hydroxyl at the C-2 atom from equatorial to axial orientation increases the stereochemically allowed region as well as the possible binding modes. From these studies it is also suggested that the overall shape of the oligosaccharides rather than the terminal or internal mannose alone affects the binding potency of saccharides to concanavalin A.