| Project/Area Number |
15K07894
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Physical pharmacy
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| Research Institution | Kobe Pharmaceutical University (2016-2018)
Gifu Pharmaceutical University (2015) |
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Principal Investigator |
Okuda Kensuke 神戸薬科大学, 薬学部, 教授 (00311796)
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| Co-Investigator(Kenkyū-buntansha) |
永澤 秀子 岐阜薬科大学, 薬学部, 教授 (90207994)
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| Research Collaborator |
TAKAGI akira 神戸薬科大学, 薬学部, 特任助教 (00758980)
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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 |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | イメージング / 蛍光 / シグナル伝達 / 分析科学 / 高感度化 / 硫化水素 / 薬学 |
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| Outline of Final Research Achievements |
We designed a turn-on type H2S fluorescent probe utilizing a coumarin fluorophores. We expected that this molecule would amplify the H2S and fluorescent signal in a chain reaction through a H2S selective deprotection reaction to result in highly sensitive H2S detection. First, we prepared the coumarin structure by the Pechmann condensation from commercially available 2-methylresorcinol. Then the protection of the hydroxy group by the TBDMS group, radical bromination at the benzylic position, and introduction of thioester moiety accompanying with deprotection of the TBDMS group were performed sequentially. Finally, we installed H2S selective responsive groups to the hydroxy group to yield desired target probes. We also started synthesis of xanthene pigments which the O atom at the 10-position substituted to other atoms to exploit advantageous near-infrared fluorescence for bioimaging, then accomplished the preparation of the key intermediates.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、酸化ストレス応答等においてNO、CO、H2Sそれぞれ単独の働きのみならず、これら分子のクロストークによる様々な生体制御が近年明らかになってきたが、細胞内でのこれら活性種の時空間的な制御に関しては不明である。
そこで、このようなクロストークの機構と生理的意義を明らかにするべく、これら活性種の個々に対応する複数の蛍光プローブを用いて蛍光顕微鏡により観察するマルチカラーイメージングの基盤を確立するべく研究を行った。H2Sが関わるクロストークを明らかにできれば、ガス状シグナル分子を基軸とする生命システムの制御機構解明研究に大きく貢献し、発がんや生活習慣病など様々な疾病治療に波及効果をもたらす。
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