Multivalent Saccharide Display on Beads Alters the Ligand Preference

The role of ligand presentation in affinity is also highlighted by the fact that functional affinity trends observed with monovalent ligands do not necessarily mirror the effects observed when these ligands are assembled into multivalent displays. Seeking to identify highly active monovalent ligands, Kahne and colleagues developed a combinatorial synthesis yielding a library of disaccharide ligands on TentaGel beads [38]. A mixed population of the beads was assayed for activity against peroxidase-labeled Bauhinia purpurea lectin (also a hemagglutinin). Beads bearing the two most active ligands identified from the library, compounds 21a and 22a, were shown to have significantly higher functional affinities than beads bearing the known Bauhinia purpurea ligand Gal^1,3GalNAc, compound 23a (Fig. 17). However, when the monovalent analogs were tested in competition experiments inhibiting Bauhinia purpurea lectin binding to Gal^1,3GalNAc-coated beads (23a), known ligand 23b was more active than the two best compounds from the library, 21b and 22b. One interpretation of these results is that ligand presentation on the beads altered the relative potencies of the ligands; however, other factors, such as saccharide residue density

Bauhinia Purpurea Side EffectsBauhinia Purpurea Side Effects
Figure 16 Roy's bi-, tri-, and tetravalent ligands 18, 19, 20 all demonstrated similar potencies on a per-saccharide basis for ConA.
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