| Project/Area Number |
18K14664
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 43040:Biophysics-related
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 人工脂質ラフト / 錯体脂質 / 細胞膜 / 境界領域 / 錯体化学 / 膜透過性ペプチド / 直接膜透過 / 脂質パッキング |
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| Outline of Final Research Achievements |
Elucidation of the mechanism underlying the direct membrane permeation of a cell-permeating peptide, R8, is an important issue in improving drug delivery technologies. The applicant hypothesized that R8 utilizes lipid rafts as a scaffold to flow into cells from the boundary region between rafts and non-rafts. First, the applicant succeeded in constructing a stable raft on the cell membrane using a complex lipid. Then, it was found that the lipid packing at local regions on the cell membrane was tightened due to the raft construction. The observation of intracellular influx of R8 revealed that the membrane permeation of R8 might be governed by multiple factors.
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| Academic Significance and Societal Importance of the Research Achievements |
革新的な新薬の創生には、細胞の膜表面分子だけでなく細胞内分子を標的とした薬物送達技術の向上が極めて重要である。細胞膜透過性ペプチドは直接膜透過によって効率的に細胞内へ分子を送達できる反面、送達可能な積荷分子にサイズ制限がある。膜透過機序が解明されれば、細胞内送達が可能な化合物の幅が広がるだけでなく、膜透過しやすい薬物の性質に関する知見が得られる。また、効率的な薬物の送達支援ツール開発においてもその根底にある機序解明に関する基礎研究が必要不可欠である。
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