Poster abstracts

Poster number 48 submitted by Prabesh Gyawali

A Single Molecule Study of the Impact of Small Molecules on Intermolecular G-Quadruplex Formation

Prabesh Gyawali (Department of Physics, Kent State University, Kent, OH, USA ), Keshav GC (Department of Chemistry and Biochemistry, Kent State University, OH, USA ), Yue Ma (Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Tokyo), Sanjaya Abeysirigunawardena (Department of Chemistry and Biochemistry, Kent State University, OH, USA ), Kazuo Nagasawa (Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Tokyo), Hamza Balci (Department of Physics, Kent State University, Kent, OH, USA )

Abstract:
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.

Keywords: G-quadruplex, Small Molecule , FRET