Monosaccharidic mimetics of the sialyl lewis(x) tetrasaccharide based on 2,7-dihydroxynaphthalene

A potential monosaccharidic mimetic of the sialyl Lewis(X) tetrasaccharide (sLe(X)) was identified based on an in silico docking study using the crystal structure of an E-selectin-sLe(X) complex. The chemical synthesis of the mimetic in an ortho-selective C-glycosylation is described. This compound and two close analogues were evaluated in a cell-based selectin binding assay where none of the tested mimetics showed an IC50 below 1mM. This result can be explained by an unexpected C-1(4) conformation of the mannosyl residue which precludes the required binding of the Ca2+-ion in E-selectin