| Project/Area Number |
18K18976
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 27:Chemical engineering and related fields
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| Research Institution | Kobe University |
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Principal Investigator |
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2019: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
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| Keywords | 自己組織化 / ペプチド脂質 / 抗ガン活性 / 選択性 / 細胞内合成 / 抗ガン剤前駆体 / リン酸化 / キナーゼ / 選択的細胞死滅 / ガン細胞 / 酵素 / 選択的細胞死 / 界面活性剤 |
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| Outline of Final Research Achievements |
We conjectured that a novel anti-cancer drug can be produced based on the enzymatic reaction inside the cancer cells. We adopted A431 cells as target cancer cells, which overexpressed tyrosine kinase. Various peptide amphiphiles were synthesized using Fmoc peptide synthesis chemistry. One of the peptide amphiphiles, 16-E4Y, exhibited remarkable cytotoxicity selective to A431 cells. The MALDI-TOF/MS analysis of cell lysate revealed that 16-E4Y was phosphorylated to be 16-E4pY inside A431 cells. These results indicate a relationship between intracellular kinase activity and the cytotoxicity of 16-E4Y. Gelation tests revealed that 16-E4pY were more likely to self-assemble to form nanofibers than 16-E4Y. The kinase activity overexpressed in cancer cells can be available for producing the selective anti-cancer activity inside the cancer cells.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、これまで用いられてきた抗ガン剤は使用せず、ペプチドと脂肪酸鎖から構成されるペプチド脂質自身が細胞内で変換されて抗ガン剤となるよう工夫した。特に、ガン細胞内で過剰発現している酵素を用いて、細胞内で抗ガン剤を作り出すよう抗ガン剤前駆体となるペプチド脂質デザインした。本手法はペプチド脂質の画期的な利用法となると同時に、このような作用機序であれば他のガン細胞にも応用が可能であるため、より効果的な抗ガン剤の開発に貢献できる可能性がある。
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