| Project/Area Number |
16K21138
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biomolecular chemistry
Chemical biology
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| Research Institution | Osaka University |
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Principal Investigator |
Higuchi Yusuke 大阪大学, 産業科学研究所, 助教 (10723439)
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| Research Collaborator |
Ohkanda Junko
Ottmann Christian
Kahn Michael
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | フシコクシン / ケミカルバイオロジー / アフィニティー精製 / タンパク質間相互作用 |
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| Outline of Final Research Achievements |
This study was carried out to identify the intracellular target of a class of diterpene glycosides, fusicoccins (FCs), which stabilizes protein-protein interaction by affinity purification. As a result, it was shown that the target protein could be captured even by a molecule using a rigid linker instead of a soft linker such as polyethylene glycol chain usually used for affinity purification. In addition, by molecular design utilizing molecular dynamics simulation, we found an FC derivative that is more active than natural FC. It has been nearly 50 years since FC was isolated, however, no compound has ever been reported that exceeds the activity of natural products. This method provide a way to develop FC based bioactive agents such as anticancer drugs.
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| Academic Significance and Societal Importance of the Research Achievements |
FCが標的とする14-3-3タンパク質は非常に多くのタンパク質と相互作用する。そのため、FCは、抗がん活性や神経細胞突起伸長作用を有することが知られているが、その作用基序は完全には解明されていない。本研究によって見出された手法は、FCが細胞内でどのタンパク質と14-3-3タンパク質との相互作用が安定化しているのかを知るためのツールとして利用できる。
また、FCが単離されてから50年近く経つが、天然物の活性を上回る化合物はこれまで報告されておらず、この知見に基づく抗がん剤開発などの展開が期待される。
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