Research topics

An international collaborative research on hydration of G-quadruplex published in Analytical Chemistry as Supplemental Cover

An international joint research paper by Dr. Saki Matsumoto, Assistant Professor, Dr. Shuntaro Takahashi, Associate Professor, and Dr. Naoki Sugimoto, Director and Professor of Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, and Calcutta University, India, has been published in Analytical Chemistry, a journal of the American Chemical Society. The paper was also selected as the Supplemental Cover of the issue of the paper.

Molecules dissolved in water are stable in solution when they interact (hydrate) with surrounding water molecules. When molecules bind to each other, changes in hydration occur, such as the removal of surface hydration. In an environment where various molecules are dissolved in high concentrations (molecular crowding environment), such as inside a cell, hydration changes and interactions between molecules also change. It has become clear in recent years that nucleic acids (DNA and RNA) form quadruplexes, which plays a role in regulating gene expression levels. In previous studies, FIBER has developed compounds that bind to the G-quadruplex of nucleic acids and regulate gene expression, but the hydration mechanism related to the G-quadruplex was still unknown.

In this study, FIBER’s Assistant Professor Matsumoto, Associate Professor Takahashi, Director and Professor Sugimoto, in collaboration with Dr. Sudipta Bhowmik of Calcutta University, India, measured the amount of hydration of the G-quadruplex using a combination of thermodynamic analysis under high pressure and molecular dynamics simulations. They found that the core G4 helix was significantly more dehydrated than the other parts, including the edges of G-quartets and loops. It was inferred that the compound bound to the core region exhibits a binding mode that is less affected by hydration. In fact, analysis of the binding of netropsin, an antibiotic compound that binds to the core of the G-quadruplex, showed that the binding behavior of netropsin was not affected by the molecular crowding environment. This method of predicting how a compound binds to the G-quadruplex within the cell is unprecedented and is expected to be used for the development of new drugs and other applications.

This research was also conducted as part of the JSPS Core-to-Core Program, a research project funded by the Japan Society for the Promotion of Science (JSPS).

The link to Anal. Chem. is here.

The paper was published in “Volumetric Strategy for Quantitatively Elucidating a Local Hydration Network around a G-Quadruplex”.
S. Matsumoto, S. Takahashi, S. Bhowmik, T. Ohyama, and N. Sugimoto, Anal. Chem. 94, 7400-7407 (2022)

FIBER will continue to contribute to the promotion of science and technology through research and development in the field of biochemistry, and to social contribution through research results.