Enzymatic synthesis of alpha3'sialylated and multiply alpha3fucosylated biantennary polylactosamines. A bivalent [sialyl diLex]-saccharide inhibited lymphocyte-endothelium adhesion organ-selectively

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Abstract
Multifucosylated sialo-polylactosamines are known to be high affinity ligands for E-selectin. PSGL-1, the physiological ligand of P-selectin, is decorated in HL-60 cells by a sialylated and triply fucosylated polylactosamine that is believed to be of functional importance. Mimicking some of these saccharide structures, we have synthesized enzymatically a bivalent [sialyl diLex]-glycan, Neu5Acα2-3′Lexβ1-3′Lexβ1-3′(Neu5Acα2–3′Lexβ1-3′Lexβ1-6′)LN [where Neu5Ac is N-acetylneuraminic acid, Lex is the trisaccharide Galβ1-4(Fucα1-3)GlcNAc and LN is the disaccharide Galβ1-4GlcNAc]. Several structurally related, novel polylactosamine glycans were also constructed. The inhibitory effects of these glycans on two l-selectin-dependent, lymphocyte-to-endothelium adhesion processes of rats were analysed in ex-vivo Stamper–Woodruff binding assays. The IC50 value of the bivalent [sialyl diLex]-glycan at lymph node high endothelium was 50 nm, but at the capillaries of rejecting cardiac allografts it was only 5 nm. At both adhesion sites, the inhibition was completely dependent on the presence of fucose units on the sialylated LN units of the inhibitor saccharide. These data show that the bivalent [sialyl diLex]-glycan is a high affinity ligand for l-selectin, and may reduce extravasation of lymphocytes at sites of inflammation in vivo without severely endangering the normal recirculation of lymphocytes via lymph nodes.