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.

Autorentext
James A. Parise Jr, PhD, is an Instructor and the Manager of the Organic Chemistry Laboratories at Duke University in Durham, North Carolina. He received his PhD in organic chemistry at Duke University in 2007 under the direction of Eric Toone and did his postdoctoral work with David Lawrence at the University of North Carolina at Chapel Hill.

Klappentext
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.