Glycan specificity of myelin-associated glycoprotein and sialoadhesin deduced from interactions with synthetic oligosaccharides

Myelin-associated glycoprotein (MAG) and sialoadhesin (Sn) bind to sialylat ed glycans on cell surfaces and are thought to be involved in cell-cell int eractions. In order to investigate how the interactions of these proteins a re influenced by the glycan structure, we compared the inhibitory potencies of different synthetic monovalent oligosaccharides and polyvalent polyacry lamide derivatives. Using oligosaccharides with modifications in the sialic acid, galactose or N-acetylglucosamine moieties, we could demonstrate that both MAG and Sn bind with high preference to alpha 2,3-linked sialic acid and interact at least with the three terminal monosaccharide units. For MAG , contacts with even more distant monosaccharides are likely, since pentasa ccharides are bound better than trisaccharides, Also, an additional sialic acid at position six of the third-terminal monosaccharide unit enhances bin ding to MAG, whereas it does not influence binding to Sn significantly. Mod ifications of the sialic acid glycerol side chain demonstrated that the hyd roxy groups at positions 8 and 9 are required for binding to both proteins. Surprisingly, MAG binds 2-keto-3-deoxy-D-glycero-D-galncto-nononic acid si gnificantly better than N-acetylneuraminic acid, whereas Sn prefers the lat ter structure. These results indicate that the interactions of MAG and Sn a re mainly with sialic acid and that additional contacts with the subtermina l galactose and N-acetylglucosamine residues also contribute to the binding strength, although to a lesser degree.