Molecule selection and optimization of highly active antisense DNA and determination of absolute configuration of phosphorus atoms
| Project/Area Number |
15H03839
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bio-related chemistry
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
WADA TAKESHI 東京理科大学, 薬学部生命創薬科学科, 教授 (90240548)
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| Research Collaborator |
Suzuki Tsutomu
Yokota Takanori
Hara Rintaro
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2018: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2016: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2015: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
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| 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 / ホスホロチオエートDNA / リン原子修飾核酸 / 立体選択的合成 |
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| 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.
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| 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。
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Report
(5 results)
Research Products
(55 results)
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[Journal Article] Solid-Phase Synthesis of Fluorinated Analogues of Glycosyl 1-Phosphate Repeating Structures from Leishmania using the Phosphoramidite Method2018
Author(s)
Rintaro Iwata Hara, Aya Yaoita, Katsuya Takeda,Hiroaki Ueki, Ayumu Ishii, Hideyuki Imoto, Satoshi Kobayashi,Michi Sano, Mihoko Noro, Kazuki Sato, Takeshi Wada
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Journal Title
ChemistryOpen
Volume: 7
Issue: 6
Pages: 439-446
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Chimeric Antisense Oligonucleotide Conjugated to α- Tocopherol2015
Author(s)
Nishina T, Numata J, Nishina K, Yoshida-Tanaka K, Nitta K, Piao W, Iwata R, Ito S, Kuwahara H, Wada T, Mizusawa H, Yokota T
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Journal Title
Mol Ther Nucleic Acids
Volume: 4
Pages: e220-e220
DOI
Related Report
Peer Reviewed / Open Access
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