Molecular Interactions at the Chemistry-Biology Interface

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.