Publication Date

2024

Document Type

Dissertation/Thesis

First Advisor

Nesterova, Irina V.

Degree Name

Ph.D. (Doctor of Philosophy)

Legacy Department

Department of Chemistry and Biochemistry

Abstract

Over the past decades, nucleic acids have emerged as crucial frameworks with significance in biological systems and functional material engineering. Cytosine-rich deoxyribonucleotide sequences can form quadruplex structures a.k.a. i-motifs. Recently, i-motifs have attracted scientific interest in biological and material design areas.

In this work, we systematically investigate an effect of structured and unstructured modifications such as hairpins, stems, loops and overhangs on the kinetic and thermodynamic properties of DNA i-motifs. We demonstrate that the modifications can influence i-motif’s stability and folding/unfolding rates: thus, double stranded stems and hairpins are the best at stabilizing i-motifs and increasing kinetic rates of folding. Meanwhile, unstructured loops and overhangs destabilize i-motifs and increase the rates of quadruplex unfolding.

We establish that proximity to Watson-Crick-based duplex may affect folding mechanism of i-motifs, leading to formation of stable and persistent partially folded topologies. We confirm the kinetic nature of biphasic distribution and investigate ways to control the population of kinetically-trapped conformations. We demonstrate that modifications are an essential tool for rational design of i-motif-based functional materials.

Finally, to explore the capabilities of i-motif modifications to control i-motif’s operational characteristics, we design a molecular device with maximized positive cooperativity of i-motif folding. Specifically, we guide i-motif devices to fold in a precisely defined topology and to control conformational populations advancing nanotechnological capabilities of i-motif-based sensors.

Extent

159 pages

Language

en

Publisher

Northern Illinois University

Rights Statement

In Copyright

Rights Statement 2

NIU theses are protected by copyright. They may be viewed from Huskie Commons for any purpose, but reproduction or distribution in any format is prohibited without the written permission of the authors.

Media Type

Text

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