Poster abstracts

Poster number 162 submitted by Mengkun Yang

Tetrahelical monomolecular architecture of nucleic acids probed by NMR

Mengkun Yang (Department of Chemsitry and Biochemistry, The Ohio State University), Levan Lomidze (Institute of Biophysics, Ilia State University, Tbilisi 0162, Republic of Georgia), Karin Musier-Forsyth (Department of Chemistry and Biochemistry, Center for RNA Biology, The Ohio State University, Columbus, OH 43210), Besik Kankia (Department of Chemistry and Biochemistry, Center for RNA Biology, The Ohio State University, Columbus, OH 43210)

Abstract:
We recently described a tetrahelical monomolecular architecture of nucleic acids that employs G (guanine)-quartets as a structural element. The monomeric units of the architecture, GGGTGGGTGGGTGGG (G3T) or its RNA analog, g3u, are folded in an intramolecular quadruplex with three G-quartets connected to each other by chain-reversal or propeller loops. In this architecture, the G3T or g3u monomers are stacked on each other forming an extraordinarily stable uninterrupted polymer. For instance, whereas the G3T monomer in 0.1 mM KCl melts at 55 °C, the molecule (G3T)2, consisting of six G-tetrads, melts at ~85 °C as a single cooperative unit. Based on thermodynamic and melting studies, we propose that the tetrahelical architecture consists of n G3T domains, (G3T)n, wherein the terminal G3 segments of adjacent G3T domains form G6-segments. Each G3T domain of the architecture is formed by zigzagging of G3-segments and T-loops, while the G6 segment is shared by adjacent domains and serves as a bridge between them. Here, we employ proton NMR to probe the solution structure of (G3T)2. Preliminary NMR data are consistent with formation of an uninterrupted homopolymer consisting of repetitive G-tetrads with strong structural symmetry. Specific guanine-to-inosine and DNA-to-RNA substitutions are underway, allowing detailed analysis of the (G3T)2 structure. The tetrahelical architecture has strong potential in DNA nanotechnology as a programmable alternative to a DNA duplex.

Keywords: tetrahelical, quadruplex, NMR