| Project/Area Number |
23790125
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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 |
Drug development chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
ISHIKAWA Minoru 東京大学, 分子細胞生物学研究所, 講師 (70526839)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 医薬分子設計 / タンパク質分解 / 創薬化学 / 標的タンパク質 / 神経変性疾患 / 標的分子同定 / タンパク質ノックダウン |
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| Research Abstract |
We have developed a method that induces selective degradation of target proteins by small molecules consisting of cIAP1 ligand linked to a ligand of the target protein (protein knockdown). In this study, protein knockdown was applied to target identification of bioactive small molecules, and degradation of misfolded proteins which would cause neurodegenerative disorders. As a proof of concept, a known target protein was identified with a proteome analysis using a linked molecule consisting of cIAP1 ligand and a small molecule which binds to a protein. On the other hand, molecules consisting of dyes bound to the misfolded proteins linked to cIAP1 ligand were designed and synthesized. The molecule was proved to bind a poly glutamine (polyQ) peptide, a major component of misfoled proteins, and decrease proteins which were immunostained with anti-polyQ antibody in living cells.
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