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Impact of Small Molecules on Intermolecular G-Quadruplex Formation

Department of Physics, Kent State University, Kent, OH 44242, USA
Department of Chemistry and Biochemistry, Kent State University, Kent, OH 44242, USA
Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan
Author to whom correspondence should be addressed.
Academic Editors: Liliya Yatsunyk and David Monchaud
Molecules 2019, 24(8), 1570;
Received: 9 February 2019 / Revised: 18 April 2019 / Accepted: 19 April 2019 / Published: 20 April 2019
(This article belongs to the Special Issue Recent Advances in Non-Canonical Nucleic Acid Structures)
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We performed single molecule studies to investigate the impact of several prominent small molecules (the oxazole telomestatin derivative L2H2-6OTD, pyridostatin, and Phen-DC3) on intermolecular G-quadruplex (i-GQ) formation between two guanine-rich DNA strands that had 3-GGG repeats in one strand and 1-GGG repeat in the other (3+1 GGG), or 2-GGG repeats in each strand (2+2 GGG). Such structures are not only physiologically significant but have recently found use in various biotechnology applications, ranging from DNA-based wires to chemical sensors. Understanding the extent of stability imparted by small molecules on i-GQ structures, has implications for these applications. The small molecules resulted in different levels of enhancement in i-GQ formation, depending on the small molecule and arrangement of GGG repeats. The largest enhancement we observed was in the 3+1 GGG arrangement, where i-GQ formation increased by an order of magnitude, in the presence of L2H2-6OTD. On the other hand, the enhancement was limited to three-fold with Pyridostatin (PDS) or less for the other small molecules in the 2+2 GGG repeat case. By demonstrating detection of i-GQ formation at the single molecule level, our studies illustrate the feasibility to develop more sensitive sensors that could operate with limited quantities of materials. View Full-Text
Keywords: G-quadruplex; small molecule; single molecule; FRET; biosensor G-quadruplex; small molecule; single molecule; FRET; biosensor

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Gyawali, P.; GC, K.; Ma, Y.; Abeysirigunawardena, S.; Nagasawa, K.; Balci, H. Impact of Small Molecules on Intermolecular G-Quadruplex Formation. Molecules 2019, 24, 1570.

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