The objective of this research is to understand the biophysical basis (thermodynamics, kinetics) for multivalency. Multivalency is concerned with biologically important interactions in which multiple receptors and multiple ligands interact simultaneously. The first focus of this work is to explore the synthesis and properties of groups used to join monovalent ligands (linkers) in the synthesis of multivalent ligands. A detailed understanding of these linkers will aid in the rational design of multivalent therapeutics. The second objective of this research is to understand the thermodynamics and kinetics of divalent ligands binding to divalent proteins in the solution phase and at surfaces. The major theme of this work is gaining a fundamental understanding of the physical chemistry that underlies multivalent binding. The benefits of the work include: i) biochemical characterization of a new class of water-soluble rigid-rods ii) improved understanding of the mechanism of divalent binding in solution and at surfaces iii) principles learned here can be applied to rational drug design. Lay Description: This project will improve understanding of multivalency and explore the fundamental physical chemistry underlying multivalency. Mulitvalency is important in biology and having a thorough understanding of multivalency will aid in the development of new approaches to management of infectious disease.
| Mack, Eric T; Snyder, Phillip W; Perez-Castillejos, Raquel et al. (2012) Dependence of avidity on linker length for a bivalent ligand-bivalent receptor model system. J Am Chem Soc 134:333-45 |
| Mack, Eric T; Snyder, Phillip W; Perez-Castillejos, Raquel et al. (2011) Using covalent dimers of human carbonic anhydrase II to model bivalency in immunoglobulins. J Am Chem Soc 133:11701-15 |
| Bracher, Paul J; Gupta, Malancha; Mack, Eric T et al. (2009) Heterogeneous films of ionotropic hydrogels fabricated from delivery templates of patterned paper. ACS Appl Mater Interfaces 1:1807-12 |
| Mack, Eric T; Perez-Castillejos, Raquel; Suo, Zhigang et al. (2008) Exact analysis of ligand-induced dimerization of monomeric receptors. Anal Chem 80:5550-5 |
