Selectins (E-, P-, and L-) are adhesion molecules mediating leukocyte interaction with endothelial cells. Carbohydrate partners (receptors) of selectins are mucin type glycoproteins bearing terminal tetrasaccharides SiaLex. Though all the three selectins recognize the tetrasaccharide, this interaction is several orders of magnitude less affine than the interaction with natural receptors. Fine carbohydrate specificity of selectins is different. Thus, P-selectin requires additional sulfotyrosine (sTyr) motif on receptor, whereas L-selectin needs sulfo group at O-6 of the GlcNAc moiety. As the natural selectin receptors are hardly available, we have synthesized their mimetics, polyacrylamide conjugates of oligosaccharides SiaLex, SiaLea, HSO3Lex, HSO3Lea, containing suitable labels (biotin, fluorescein, tritium). It has been shown that dissociation constants of monomeric oligosaccharides interaction are of mM level, and those of polymeric ones are of μM level. Model system where carbohydrate ligand of necessary clusterness and density is coated to artificial (glass) surface, has been developed for the study of dynamics of leukocyte interaction with carbohydrate ligands on epithelium surface (rolling).
It has been shown that carbohydrate ligand without negative charge can bind P-selectin, especially in vitro. At the same time, polymers with high negative charge density, e.g.