Figure 28 Kretzchmar's trivalent sLex conjugate.
folding. For example, trivalent glycopeptides were up to 10-fold more active than their monovalent counterparts [209,216,223].
Bivalent ligands displaying nonnatural residues, mannose biphenyl glycosides, were devised by Kogan et al.  to mimic di-sLex, an oligosaccharide that appears to bind more tightly to E-selectin than sLex. Compounds in a series with variable spacer residues connecting the mannose moieties were tested against all three selec-tins in a static cell binding assay. The most active ligand, 58, demonstrated increased potencies (ca. sixfold for E- and L-selectin) consistent with binding within a single lectin domain (Figure 29) . Trivalent ligands in this series were no more potent than their bivalent counterparts. The modest inhibitory potency increases observed with the small multivalent ligands explored to date are likely due to secondary interactions near the binding site.
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