Date of Award
Master of Science
G-quadruplex structures are higher order DNA or RNA structures formed by the association of guanine rich nucleic acid sequences. This study is focused on DNA G-quadruplex structures that have implications in many biological processes and diseases. Specific structural assignment of these structures is essential to understand their biological roles and to effectively target them with therapeutics. In this study we use a combination of Infrared (IR) and fluorescence spectroscopic techniques to characterize diverse structural conformations adopted by G-quadruplex motifs. We have employed 2D IR spectroscopy aided with site specific isotope labeling to examine the structural variations arising from heterogeneity of metal coordination. These insights have been utilized to understand how local structural variations in G-quadruplex motifs modulate the fluorescence response of Thioflavin T which is used as non-specific fluorescent probe to detect G-quadruplex motifs. It is also shown that polarization dependence of cross peaks in 2D IR spectra can be used as a spectral marker to distinguish topology of G-quadruplex structures. Finally, inosine base substitution has been employed to highlight the contribution of hydrogen bonds to stability of G-quadruplex structures. This study highlights IR spectroscopy as a powerful tool to analyze G-quadruplex structures and as a complementary tool to validate insights gain through other experimental approaches.
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