STRUCTURE-ACTIVITY-RELATIONSHIPS OF SIALYL-LEWIS X-CONTAINING OLIGOSACCHARIDES .1. EFFECT OF MODIFICATIONS OF THE FUCOSE MOIETY

Leukocyte adhesion to the vasculature is mediated by E-, P-, and L-sel ectins. The natural ligands for E- and P-selectins have not been fully characterized but have been shown to contain the tetrasaccharide sial yl Lewis x structure (Sle(x)). To determine the importance of he fucos e moiety of SLe(x), various analogs of SLe(x) containing modifications thereof were prepared and tested as inhibitors of E-selectin-mediated cell adhesion. Cellular experiments indicate that replacement of the hydroxyl groups of fucose by hydrogen abrogated E-selectin binding. Ho wever, the arabinose analog of fucose (CH3 Delta H) inhibited cell adh esion but was 5-fold less potent than native SLe(x). This data suggest s that modifications of fucose on SLe(x) are generally deleterious tow ard E-selectin binding.