Molecule selection and optimization of highly active antisense DNA and determination of absolute configuration of phosphorus atoms

2018 Fiscal Year Final Research Report

• Project/Area Number: 15H03839
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Bio-related chemistry
• Research Institution: Tokyo University of Science
• Principal Investigator: WADA TAKESHI 東京理科大学, 薬学部生命創薬科学科, 教授 (90240548)
• Research Collaborator: Suzuki Tsutomu ; Yokota Takanori ; Hara Rintaro
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 核酸医薬 / アンチセンス核酸 / ホスホロチオエート核酸 / 立体制御 / 分子選択 / 不斉合成

Outline of Final Research Achievements

Phosphorothioate nucleic acids in which sulfur atoms are introduced to internucleotidic phosphodiester linkages are widely used as nucleic acid drugs in order to enhance the stability in vivo. However, they are a mixture of numerous stereoisomers based on the chiral phosphorus atoms. In this study, we selected the molecule that is most stable in vivo and high in pharmacological activity among many stereoisomers, and established the basic principle of the method for determining the absolute configuration of the phosphorus atoms. Further improvement of this method can be expected to lead to establishment of a technique for selecting a molecule that works most effectively as a drug in vivo and determining the absolute configuration of its phosphorus atoms.

Free Research Field

有機合成化学

Academic Significance and Societal Importance of the Research Achievements

現在、抗体医薬に続く次世代医薬として、核酸医薬の実用化に大きな期待が寄せられている。数千から数百万立体異性体の混合物である核酸医薬の中から、最も生体内で安定であり、かつ薬理活性も高い分子を選択する手法の基本原理を確立した。本技術がさらに改良されれば、核酸医薬の飛躍的な活性の向上に伴う投薬量の軽減、生産コストの削減、患者の肉体的、経済的負担の軽減、核酸医薬の安全性や品質管理の改善が期待できる。