An international collaborative research paper on the structural analysis of G-quadruplex DNA by FIBER was published in Journal of the American Chemical Society.
We are pleased to announce that an international joint research paper by Associate Professor Shuntaro Takahashi, Director and Professor Naoki Sugimoto of the Frontier Institute for Biomolecular Engineering Research (FIBER) at Konan University, and a research group from the University of Reading (UK) has been published in Journal of the American Chemical Society (JACS).
The basic structure of nucleic acids (DNA and RNA) is the double helix structure, but they also form special structures such as the quadruplex. The quadruplex includes the guanine quadruplex structure (G-quadruplex), and the topology of the quadruplex changes depending on the sequence and environment. Sequences that form these quadruplexes are often found in genes associated with cancer and neurodegenerative diseases. Therefore, drugs that can control the structure of the quadruple helix are being developed for the prevention and treatment of these diseases. However, there is a lack of information on molecular structure, which is essential for drug development, making it difficult to design rational drugs that act on the quadruple helix.
FIBER, as an international joint research center for nucleic acid chemistry, has been conducting joint research with various overseas research institutions, and this year, a research project has also started as a JSPS Core-to-Core project (see news article). In this research, Associate Professor Takahashi and Director and Professor Sugimoto of FIBER, in collaboration with research groups at the University of Reading in the U.K., have succeeded in determining the binding of a compound called a ruthenium complex to G-quadruplex DNA derived from human telomeres at the atomic level through X-ray crystallographic analysis. The newly developed compound is a ruthenium complex, which is a molecule formed when ruthenium is bound to an organic compound, and is characterized by its ability to form complex three-dimensional structures. The ruthenium complexes developed in this study have been found to induce G-quadruplex with an antiparallel topology, and to strongly stabilize the quadruplex structure. This allows DNA replication reactions to be controlled more potently than with other compounds that have been reported. The research results are expected to lead to the development of new drugs for cancer, neurodegenerative diseases, and other disorders.
The three-dimensional structure of the compound can be clearly seen in the following video;
The link to the JACS journal is here.
The paper is titled “Ruthenium Polypyridyl Complex Bound to a Unimolecular Chair-Form G-Quadruplex” and was published by K. T. McQuaid.
K. T. McQuaid, S. Takahashi, L. Baumgaertner, D. J. Cardin, N. G. Paterson, J. P. Hall, N. Sugimoto, and C. J. Cardin, J. Am. Chem. Soc., 144, 5956-5964 (2022)
The Frontier Institute for Biomolecular Engineering Research (FIBER) will continue to contribute to the advancement of science and technology and to the benefit of society through research and development in the field of biochemistry.