| Project/Area Number |
17K19203
|
|---|
| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Biomolecular chemistry and related fields
|
|---|
| Research Institution | Kyushu University |
|---|
Principal Investigator |
Ojida Akio 九州大学, 薬学研究院, 教授 (10343328)
|
|---|
| Project Period (FY) |
2017-06-30 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
|
|---|
| Keywords | 蛍光プローブ / 代謝 / がん / ベータ酸化 |
|---|
| Outline of Final Research Achievements |
In this research project, we developed the fluorescent probes that can detect the activity state of the metabolic pathways in living cells. In the research period, we focused on the development of the turn-on type fluorescent probe that can sense the activity of the fatty acid beta oxidation. The probe exploited the intramolecular cyclization of the metabolically produced thioester as a sensing mechanism. We confirmed that the probe was converted to the desired cyclized product as a result of beta oxidation and the subsequent intramolecular cyclization. This finding would provide molecular design basis for development of fluorescent probes that can detect the activity of other central metabolism pathways such as glycolysis and TCA cycle. We also developed the auto-immolative linker, which is useful in design of fluorescent probes for various enzyme-catalyzed reactions.
|
| Academic Significance and Societal Importance of the Research Achievements |
これまでに様々な細胞イベントを検出できる蛍光プローブが開発されてきたが、代謝経路自体の活性化を検出できる蛍光プローブの開発例はほとんど報告されていない状況にあった。本研究では、様々な細胞内代謝経路を検出できる可能性を持つ新しいセンシング機構を提案し、実際にそれが細胞内で機能することを明らかにした。本研究から得られた知見は、様々な代謝経路の蛍光可視化する蛍光プローブの分子デザインに有用に知見を与えるものである。また将来的には、細胞代謝の蛍光解析の実現や代謝を標的とした薬剤分子のスクリーニングにも貢献することが期待できる。
|
