Research
Faculty Members
Bioorganic Chemistry（Chemistry）
Osawa TakashiAssociate professor / Lecturer
Since starting the synthetic research on 2',4'-bridged nucleic acids in the department of bioorganic chemistry in 2009, I have been consistently advancing research related to nucleic acid chemistry. With the vigorous progress of research on the development of nucleic acid drugs targeting RNA as a therapeutic target and the increasing importance of nucleic acid chemical modification technology in recent years, I’m studying with the students belonging to Professor Obika’s laboratory. I would like to contribute to the development of nucleic acid medicine.
Research theme
Research on the synthesis of nucleic acids with fixed conformations of the sugar and phosphate moieties of oligonucleotides
Artificial nucleic acids with constrained sugar and phosphate moieties of oligonucleotides has excellent target RNA binding ability. On the other hand, artificial nucleic acids having an appropriately fixed conformation generally have a complicated structure and therefore have difficulty in synthesizing. In this study, we are designing several types of artificial nucleic acids in which the conformation of the sugar and phosphate parts is fixed by a simple bicyclic sugar part skeleton, and we are proceeding with their synthesis and evaluation of their physical properties.
Development of chemical reactions that enable the efficient supply of diverse modified oligonucleotides and their application in drug discovery.
If the structure-activity relationship of oligonucleotide medicines can be clarified, it will be possible to logically design oligonucleotide medicines. However, since the derivatization of oligonucleotides is difficult, it is necessary to develop a method that can easily and efficiently supply a wide variety of modified oligonucleotides. Against this backdrop, we are developing methods for structurally transforming only the parts of oligonucleotides that we want to chemically modify, and conducting research on their application in drug discovery.
Research on the chemistry, synthesis, and purification of oligonucleotides that suppress impurities specific to nucleic acid drugs
Development of oligonucleotide therapeutics has become increasingly active in recent years, and the importance of its CMC (chemistry, manufacturing, and quality control) is growing year by year. Chemically synthesized oligonucleotide therapeutics can produce impurities unique to oligonucleotide s due to undesirable chemical reactions between the base, sugar, and phosphate moieties during the manufacturing process. To address these challenges, we are engaged in fundamental research on the chemistry, synthesis, and purification of oligonucleotides, aiming to elucidate the impurity generation mechanism and to control impurities from the organic chemistry perspective of nucleic acids.
Representative achievements
Osawa, T.; Yamashita, R.; Koyama, H.; Fujisue, D.; Obika, S. “Amidation of phosphonoacetate-modified oligonucleotides and evaluation of the properties of the synthesized oligonucleotides” Org. Lett. 2026, in press.
Osawa, T.; Miyata, K.; Ito, S.; Uda, K.; Obika, S. “Regulation of Duplex Formation in Response to pH and Complementary RNA: Development of Oligonucleotides Modified with S-Methylthioimidate-Bridged Nucleic Acid and Evaluation of Their Function” ACS Omega 2026, 11, 3436–3447.
Osawa, T.; Nakanishi, R.; Uda, K.; Muramoto, S.; Obika, S. “Synthesis and structural analysis of dinucleotides containing 2′,3′-trans-bridged nucleic acids (2′,3′-trans-BNAs) with trans-5,6- or 5,7-fused ring skeleton” Commun. Chem. 2025, 8, 87.
Osawa, T.; Kita, R.; Kasahara, Y.; Yamaguma, H.; Nakayama, T.; Kamada, H.; Obika, S. “In vitro screening of chemically synthesized dipeptide-antisense oligonucleotide conjugates to identify ligand molecules enhancing their activity” Bioorg. Med. Chem. 2024, 110, 117814.
Ren, Q.; Osawa, T.; Tatsuno, M.; Obika, S. “THF peroxide as a factor in generating desulphurised products from the solid-phase synthesis of phosphorothioate-modified oligonucleotides” RSC Adv. 2024, 14, 21590–21596.
Huo, W.; Miki, K.; Mu, H.; Osawa, T.; Yamaguma, H.; Kasahara, Y.; Obika, S.; Kawaguchi, Y.; Hirose, H.; Futaki, S.; Miyazaki, Y.; Shinoda, W.; Akai, S.; Ohe, K. “Light-controllable cell-membrane disturbance for intracellular delivery” J. Mater. Chem. B 2024, 12, 4138–4147.
Osawa, T.; Akino, T.; Obika, S. “Synthesis, duplex-forming ability, and enzymatic stability of oligonucleotides modified with amide-linked dinucleotides containing a 3′,4′-tetrahydropyran-bridged nucleic acid” J. Org. Chem. 2024, 89, 269–280.
Ren, Q.; Osawa, T.; Obika, S. “Development of a simple purification method for oligonucleotides synthesized by using a phosphoramidite for 5'-end modification as a capping reagent” Tetrahedron 2024, 150, 133774.
Mikami, A.; Mori, S.; Osawa, T.; Obika, S. “Post-synthetic nucleobase modification of DNA by Sonogashira coupling and influence of alkynyl modifications on the duplex-forming ability” Chem. Eur. J. 2023, e202301928.
Kita, R.; Osawa, T.; Obika, S. “Conjugation of oligonucleotides with activated carbamate reagents prepared by the Ugi reaction for oligonucleotide library synthesis” RSC Chem. Biol. 2022, 3, 728–738.
