Research
Faculty Members
Bioorganic Chemistry（Chemistry）
Obika SatoshiProfessor
PRESENT ACADEMIC POSITION
1992—2006 Assistant Professor, Graduate School of Pharmaceutical Sciences, Osaka University
2006—2008 Associate Professor, Graduate School of Pharmaceutical Sciences, Osaka University
2004—2008 PRESTO (Precursory Research for Embryonic Science Technology) Research Fellow, JST (Japan Science and Technology Agency)
2008— Professor, Graduate School of Pharmaceutical Sciences, Osaka University
2012—2018 Education and Research Council Member, Osaka University
2013—2018 Director, Drug Innovation Center, Graduate School of Pharmaceutical Sciences, Osaka University
2013— Project Leader, National Institutes of Biomedical Innovation, Health and Nutrition
2021— Education and Research Council Member, Osaka University
2021— Director, Drug Innovation Center, Graduate School of Pharmaceutical Sciences, Osaka University
EDUCATION AND RESEARCH EXPERIENCE
1986—1990 B. S. Faculty of Pharmaceutical Sciences, Osaka University, Japan
1990—1992 M. S. Graduate School of Pharmaceutical Sciences, Osaka University, Japan
1998- Ph. D. in Pharmaceutical Sciences (Graduate School of Pharmaceutical Sciences, Osaka University)
2002—2003 Visiting Researcher, Department of Chemistry and Biochemistry, University of California Santa Barbara, Santa Barbara, CA
Our laboratory conducts a wide range of research on " oligonucleotide therapeutics," one of the new drug discovery modalities, from molecular design to synthesis and evaluation of biological functions. There are still many diseases that are difficult to cure even with current medical science. It is our great mission to advance the research and development of oligonucleotide therapeutics to develop treatments for intractable diseases. We will continue our daily research without forgetting that there are patients who are waiting for the results of our research to be released to the world.
Research theme
Synthetic Studies of Functional Artificial Nucleic Acids
Nucleic acid molecules cannot be used as-is as pharmaceuticals because they are very easily degraded in vivo. The molecular design and synthesis of artificial nucleic acids with improved in vivo stability and binding affinity to target RNA is an important part for the development of oligonucleotide therapeutics. We are focusing on the design and synthesis of artificial nucleic acids not only to improve the efficacy but also to enhance safety.
Research on Artificial Nucleic Acids for Pharmaceutical Applications
Sequence design is also important in the development of oligonucleotide therapeutics. Sequence design is performed from various perspectives, such as which region of the target RNA to target with oligonucleotide therapeutics and of what length, and the number and position of the artificial nucleic acids to be introduced in this process. The function (efficacy, safety, etc.) of the oligonucleotide therapeutics is evaluated in in vitro and in vivo experiments, and the results are fed back to the development of new artificial nucleic acids and sequence design.
Development of Technology for Controlling the PK/PD Profiles of oligonucleotide therapeutics
When oligonucleotide therapeutics that have shown efficacy at the cellular level are made into pharmaceuticals, it is necessary to deliver the oligonucleotide therapeutics to the targeted organs. We are working on the development of DDS technology by applying appropriate chemical modifications to oligonucleotide therapeutics and taking the approach of evaluating their efficacy in specific organs and also comparing effects between organs.
Representative achievements
Synthesis, Duplex-forming Ability, and Nuclease Resistance of Oligonucleotides Containing A Thymidine Derivative with A 1-Oxaspiro[4.5]decane Skeleton
T. Osawa, N. Yano, H. Aoyama, S. Obika
Chem. Pharm. Bull., 2022, 70, 699-706.
Synthesis and Physical and Biological Properties of 1,3-Diaza-2-oxophenoxazine-conjugated Oligonucleotides
R. Yamaji, O. Nakagawa, Y. Kishimoto, A. Fujii, T. Matsumura, T. Nakayama, H. Kamada, T. Osawa, T. Yamaguchi, S. Obika
Bioorg. Med. Chem., 2022, 72, 116972.
Conjugation of Oligonucleotides with Activated Carbamate Reagents Prepared by The Ugi Reaction for Oligonucleotide Library Synthesis
R. Kita, T. Osawa, S. Obika
RSC Chem. Biol., 2022, 3, 728-738.
Structure-activity Relationships of Anti-microRNA Oligonucleotides Containing Cationic Guanidine-Modified Nucleic Acids
T. Takegawa-Araki, S. Kumagai, K. Yasukawa, M. Kuroda, T. Sasaki, S. Obika
J. Med. Chem., 2022, 65, 2139-2148.
Physicochemical Property Evaluation of Modified Oligonucleotides by Traveling-Wave Ion Mobility Mass Spectrometry
S. Omuro, T. Yamaguchi, T. Kawase, M. Terasaki, K. Hirose, S. Obika
Rapid Commun. Mass Spectrom., 2022, 36, e9279.
Reduction of Off-target Effects of Gapmer Antisense Oligonucleotides by Oligonucleotide Extension
H. Yasuhara, T. Yoshida, K. Sasaki, S. Obika, T. Inoue
Molecular Diagnosis Therapy, 2022, 26, 117-127
Identification of Nucleobase Chemical Modifications That Reduce The Hepatotoxicity
of Gapmer Antisense Oligonucleotides
T. Yoshida, K. Morihiro, Y. Naito, A. Mikami, Y. Kasahara, T. Inoue, S. Obika
Nucleic Acids Res., 2022, 50, 7224-7234.
Enhanced Duplex- and Triplex-forming Ability and Enzymatic Resistance of Oligodeoxynucleotides Modified by a Tricyclic Thymine Derivative
Y. Kishimoto, A. Fujii, O. Nakagawa, S. Obika
Org. Biomol. Chem., 2021, 19, 8063-8074.
Synthesis and Duplex-forming Ability of Oligonucleotides Modified with 4′-C,5′-C-Methylene-bridged Nucleic Acid (4′,5′-BNA)
T. Yamaguchi, C. Yamamoto, M. Horiba, H. Aoyama, S. Obika
Bioorg. Med. Chem., 2021, 46, 116359.
Synthesis and Properties of Oligonucleotides Modified with N-Methylguanidine-bridged Nucleic Acid (GuNA[Me]) Bearing Adenine, Guanine, or 5-Methylcytosine Nucleobase
N. Horie, T. Yamaguchi, S. Kumagai, S. Obika
Beilstein J. Org. Chem., 2021, 17, 622-629.
