Quantitative Analysis of Nucleic Acid Stability with Ligands Under High Pressure to Design Novel Drugs Targeting G‐Quadruplexes

Abstract

Nucleic acids (DNA and RNA) can form various non-canonical structures. Because some serious diseases are caused by the conformational change of G-quadruplex DNA structures, the development of ligands that bind and stabilize G-quadruplex DNA is of interest to the field of nucleic acid chemistry. Volumetric changes (ΔV) in the biomolecular reaction include the structural change of biomolecules and hydration behaviors, which provide information about the tertiary interaction between G-quadruplex DNA and ligands. Thus, it is valuable to investigate ΔV values to understand the mechanism of interaction between non-canonical structures and their ligands. This unit describes methods that can be used to quantitatively analyze the interaction between G-quadruplex DNA and ligands by using high-pressure UV melting. The combination of thermodynamic parameters (ΔG, ΔH, ΔS, and ΔV) is a powerful tool to elucidate the mechanism of ligand binding to G-quadruplex without real structural analysis by NMR and X-ray spectroscopy, and gives useful information to design novel drugs. © 2017 by John Wiley & Sons, Inc.

Volumetric Strategy for Quantitatively Elucidating a Local Hydration Network around a G-Quadruplex

“…The setup of UV spectroscopy with a high-pressure equipment system was described previously. , Briefly, the high-pressure optical unit PCI-500 from Syn Corporation (Kyoto, Japan) was installed in a Shimadzu UV-1700 spectrometer. The temperature and pressure inside the optical unit were controlled using an F-25-ME circulator from Julabo (Seelbach, Germany) and a PV-400 pressure reservoir (Syn Corporation).…”

Lighting Up of Thiazole Orange on G-Quadruplex DNA by High Pressure

“…One of the possible methodologies is pressure change. Pressure control is a physical treatment, which does not need to add and remove chemical compounds to control the structures of ligand and G-quadruplex. − Increasing pressure decreases the volume of molecules represented as partial molar volumetric change Δ V (cm 3 mol –1 ). We have reported that Δ V of hemin binding to human telomeric G-quadruplex DNA (termed h-telo here) having a mixed topology showed a smaller value than the value of that binding to the antiparallel h-telo .…”