In this project funded by the Macromolecular, Supramolecular and Nanochemistry Program of the Chemistry Division, Ken Shimizu of the University of South Carolina will study the ability of anions to stabilize and destabilize protein structures. The strategy is use a "molecular balance," a small molecule model system that can measure and provide molecular-level insight into the interactions of anions with individual amino acid side chains. These molecular balances are in equilibrium between folded and unfolded conformers. In the folded conformers, amino acid side-chains in the balances form intramolecular hydrophobic and non-covalent interactions with a hydrophobic aromatic shelf. In the unfolded conformers, these intramolecular interactions are broken. Thus, the influence of anions on these non-covalent interactions can be quantitatively measured by monitoring the folded/unfolded ratios using NMR spectroscopy. The balances are assembled in a modular fashion, allowing the rapid synthesis of a series of balances containing different amino acid side chains, water solubilizing groups, and various hydrophobic surfaces. The proposed balances also contain fluorine NMR labels that provide more accurate measurements and enable their study within complex heterogeneous environments. The broader scientific impact of this project will be the development of new strategies and methods for stabilizing and solubilizing proteins. Additional activities pursued during this project will be: 1) to develop a free website to help undergraduate students to study organic chemistry, 2) to provide research opportunities for groups underrepresented in chemistry, and 3) to perform chemistry demonstrations at area K-6 classes and to participate in the SCienceLab program that brings middle and high school classes to the university for a hands-on laboratory experience.
Proteins are biological molecules that perform critical structural and active functions in biological systems. These studies will provide molecular-level insights into how proteins and segments of proteins interact with each other as well as how the fold into complex structures. A net result of this research will be to enable new strategies and methods for stabilizing and solubilizing proteins. Such work will have applications in enhancing the shelf lives of protein- and antibody-based pharmaceuticals and as well as assisting in the development of biosensors and new pharmaceuticals.
