2012 Fiscal Year Final Research Report
Novel strategy for medicinal chemistry utilizing protein knockdown
| 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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| Keywords | 医薬分子設計 / タンパク質分解 |
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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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Research Products
(10 results)
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[Presentation] Development of small molecules that induce IAP-mediated ubiquitylation and proteasomal degradation of target proteins, The Sixth International Conference SUMO, Ubiquitin2012
Author(s)
Mikihiko Naito, Keiichiro Okuhira, Nobumichi Ohoka, Norihito Shibata, Takayuki Hattori, Yukihiro Itoh, Minoru Ishikawa, Yuichi Hashimoto
Organizer
UBL Proteins:Implications for Human Diseases
Place of Presentation
Houston, TX, United States ofAmerica
Year and Date
20120208-0211
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[Presentation] Development of Hybrid Small Molecules That Induce IAP-Mediated Ubiquitylation and Proteasomal Degradation of Target Proteins in a Specific Manner
Author(s)
Mikihiko Naito, Keiichiro Okuhira, Yosuke Demizu, Yukihiro Itoh, Minoru Ishikawa, Nobumichi Ohoka, Norihito Shibata, Takayuki Hattori, Tomoko Nishimaki-Mogami, Masaaki Kurihara, Yuichi Hashimoto
Organizer
Cell Symposia: Genetics and Chemistry Sharing a Language of Discovery
Place of Presentation
Cambridge, MA, United States of America
Year and Date
00000523-0525
