Studies on molecular analysis of cell adhesion mediated by carbohydrate recognitions

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The selectins are a family of carbohydrate-binding proteins (C-type lectin) involved in leukocyte trafficking, thrombosis, inflammation, tumor metastasis, and so on. In this study, we have demonstrated the mechanism of cell adhesion mediated by selectins not only on the molecular level but also on the level of functional groups by using synthetic sialyl Lewis X and a variety of the analogs. As a result, it has been concluded that : (1) For the binding face of the sialyl Lewis X epitope interacting with E-selectin, the carboxyl group of sialic acid, the 4- and 6-hydroxyls of galactose, and the 2-, 3-, and 4-hydroxyls of fucose are involved in selectin-carbohydrate binding, and further, the fucose moiety is directly involved in the calcium dependency ; (2) Based on the comparison with sulfatide, the roles of carboxyl and sulfate groups, and the presence of the basic amino acids as the counterparts have strongly been suggested ; (3) As the most important finding of the current results, the first total syntheses of the sulfated sialyl Lewis X pentasaccharide gangliosides revealed that the binding of human L-selectin to the 6-0-sulfo (in the GlcNAc moiety) sialyl Lewis X is much stronger than that of sialyl Lewis X,suggesting the possibility of the receptor specificity control by sulfation cappings. In addition, the binding of E-selectin was lost by the 6'-O-sulafation (in the Gal moiety). All these results are the first findings in the world.On the other hand, in a series of studies on clarifying the recognition specificity of sialoadhesin family (I-type lectin), we have demonstrated that ganglioside GQ1balpha is one of the strongest carbohydrate ligands for the binding of myelin-associated glycoprotein (MAG).