| Summary: | My thesis research spread across the two major areas of venom protein toxin research. In the therapeutic research area, I focused on the studies of ShK toxin as this protein molecule has been suggested as therapeutic candidate for treatment of autoimmune diseases. My research established a more efficient chemical synthesis strategy for the ShK protein molecule and we used racemic protein crystallography to characterize its X-ray crystal structure. Chemical protein synthesis also made it possible for me to generate unnatural amino acid containing ShK analogs to study the impact of subtle structure change on ShK protein molecule foldability, stability, and biological activity. In the biophysical probe development area, I focused on developing Ts1 toxin and Ts3 toxin protein molecules to be voltage-gated sodium channel probes. Chemical protein synthesis enabled by native chemical ligation really is the key to the success of my research. Using chemical protein synthesis, I was able to produce Ts1 and Ts3 polypeptide chains with high yield and purity within relatively short periods of time. The modular synthetic strategy also enabled me to prepare different analogs of these protein molecules to determine the true identity of the bioactive toxin. The ability to chemically prepare these protein molecules gave us the power to modify the protein structure based on our need and we were able to incorporate unnatural amino acids bearing unique reactive moieties into specific sites within the protein molecules for the attachment of different reporter molecules. These chemically developed probes were then used for different applications including sodium channel structure studies and photostimulation of neurons.
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