Functional analysis of g-secretase, which concerned with generation of amiroide-b-pepilde1
| Project/Area Number |
17590003
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemical pharmacy
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| Research Institution | University of Shizuoka |
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Principal Investigator |
KAN Toshiyuki University of Shlitioka, School of Pharmaceutical science, Professor, 薬学部, 教授 (10221904)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | γ-secretase / Alzheimer's disease / DAPT / photoaffinity probe / photoaffinity labeling / PS1 CTFs / familial AD / competing photolabeling / フォトアフィニティプローブ / 光親和性ラベリング / リガンド分子 / 光反応性基 / ビオチン / Ns-Strategy / βアミロイド産出 / PS1CTF |
|---|
| Research Abstract |
We investigated the screening of a potent inhibitor and the functional analysis of y-secretase, which was identified as an important therapeutic target for Alzheimer's disease (AD). During the course of our investigation based on potent inhibitor DAPT (1), we developed a fitile synthetic method for a photoaffinity probe by utilizing the polymer-bound reagent. Furthermore, the utility of the reagent was demonstrated by synthesis of the probe and the photoaffinity labeling experiments of the probe clarified that the major direct target molecules for the DAPT are preseniline 1 C-terminal fragments (PS1 CTFs), which were discovered from the genetically investigation of familial AD. Additionally, a competing photolabeling experiment of the probe against various class of inhibitors, we dissected the inhibitory mechanism of DAPT.
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Report
(3 results)
Research Products
(27 results)
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[Journal Article] Divergent Synthesis of Multifunctional Molecular Probes Enabled Elucidation of the Enzyme Specificity of Dipeptidic γ-Secretase Inhibitors on Presenilin-Type Aspartic Proteases2007
Author(s)
H.Fuwa, Y.Takahashi, Y.Konno, N.Watanabe, H.Miyashita, M.Sasaki, H.Natsugari, T.Kan, T.Fukuyama, T.Tomita, T.Iwatsubo
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Journal Title
ACS Chemical Biology (in press)
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Novel g-secretase inhibitors discovered by screening in-house natural product synthesis intermediates library2006
Author(s)
Y.Takahashi, H.Fuwa., A.Kaneko, M.Sasaki, S.Yokoshima, H.Koizumi, T.Takebe, T.Kan, T.Iwatsubo, T.Tomita, H.Natsugari, T.Fukuyama
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Journal Title
Bioorg. Med. Chem. Lett. 16
Pages: 3813-3813
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] Novel y-secretase inhibitors discovered by screening in-house natural product synthesis intermediates library2006
Author(s)
Y.Takahashi, H.Fuwa, A.Kaneko, M.Sasaki, S.Yokoshima, H.Koizumi, T.Takebe, T.Kan, T.Iwatsubo, T.Tomita, H.Natsugari, T.Fukuyama
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Journal Title
Bioorg. Med. Chem. Lett. 16
Pages: 3813-3816
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Novel g-secretase inhibitors discovered by screening in -house natural product synthesis intermediates library2006
Author(s)
Y.Takahashi, H.Fuwa, A.Kaneko, M.Sasaki, S.Yokoshima, H.Koizumi, T.Takebe, T.Kan, T.Iwatsubo, T.Tomita, H.Natsugari, T.Fukuyama
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Journal Title
Bioory. Med. Chem. Lett. 16
Pages: 3813-3813
Related Report
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[Journal Article] Reaction behavior of cumulene on Diels-Alder and Friedel-Crafts reaction2006
Author(s)
Asakawa, T., Iinuma, M., Furuta, T., Fujii, S., Kan, T., Tanaka, K.
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Journal Title
NAID
Related Report
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[Journal Article] Carboxy-terminal fragment of Presenilin 1 is the molecular target of a dipeptidic y-secretase-specific inhibitor DAPT2006
Author(s)
Morohashi, Y., Kan, T., Tominari, Y., Fuwa, H., Okamura, Y., Watanabe, N., Natsugari, H., Fukuyama, T., Iwatsubo, T., Tomita T.
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Journal Title
Related Report
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