MOLECULAR INTERACTIONS AT THE CHEMISTRY-BIOLOGY INTERFACE: The Design of Interfacial Biomaterials and the Modulation of Galectin-3 Aggregation With Multivalent Saccharide Ligands

Myriad biological processes are governed by chemical reactions that occur on cell surfaces. In the first part of this work, a novel approach to direct biological processes that occur at the surface of artificial materials is described. A multi-faceted strategy has been developed to construct ¿interfacial biomaterials¿ that mediate specific biological processes via increased cellular adhesion to medically-relevant materials. A phage display selection strategy was developed to identify peptides that show increased affinity for natural and artificial substrates. In the second part, the molecular basis of protein¿carbohydrate binding is considered. Ligands displaying lactose epitopes were constructed to investigate their aggregative properties towards full¿length and truncated galectin¿3. ITC studies with full¿length protein shows a greater than two¿fold enhancement in affinity for the bivalent ligand compared to monovalent ligand. This behavior demonstrates that protein-protein interactions and aggregation are the primary cause for affinity increases observed with polyvalent saccharide ligands, and unambiguously establishes a molecular basis for the cluster glycoside effect.