Date of Award
Open Access Dissertation
Chemistry and Biochemistry
College of Arts and Sciences
In this dissertation, I have used single molecule Fluorescence Resonance Energy Transfer (sm-FRET), as a nanoscale spectroscopic ruler to gain quantitative, molecular-level understanding about the kinetics and mechanism of NC-chaperoned TAR sequence rearrangements. Firstly, I have resolved the complex kinetics and underlying reaction pathways of TAR sequence annealing in the presence of HIV-1 NC over a broad NC concentration by performing the time-resolved sm-FRET measurements in a unique aggregation-free environment. I have further gained the insights that the NC-induced secondary structural changed of TAR hairpins modulate the annealing pathways and consequently affect the overall kinetics of the TAR sequence annealing. Secondly, I have demonstrate the macromolecular crowding effects on NC-chaperoned NA annealing by choosing poly-ethylene glycol as a model neutral polymer cosolute to mimic the highly crowded environment in the cytoplasm. Macromolecular crowding effects accelerates every steps in the annealing process without changing the annealing pathway, and make the NC prefer to chaperone with the double-stranded NA. These detailed understanding of the NC-facilitated minus-strand transfer step of reverse transcription of reverse transcription at molecule-level enhance our capabilities to better design effective anti-viral medications and therapies. Thirdly, I have also investigate the multifaceted gold-palladium bimetallic nanorods and their geometric, compositional and catalytic tunabilities.
Sun, L.(2017). Mechanistic Studies of Nucleic Acid Chaperone Activities of Retroviral Nucleocapsid Protein. (Doctoral dissertation). Retrieved from https://scholarcommons.sc.edu/etd/4199