| Project/Area Number |
17K18123
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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 |
Bio-related chemistry
Chemical biology
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| Research Institution | Tokai University |
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Principal Investigator |
Arai Kenta 東海大学, 理学部, 講師 (60728062)
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| Project Period (FY) |
2017-04-01 – 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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | セレン / タンパク質フォールディング / 酸化還元反応 / 神経変性疾患 / 創薬 / 酸化ストレス / 酵素モデル / フォールディング / セレネニルスルフィド / ジセレニド / 抗酸化剤 / タンパク質 / ジスルフィド / 抗酸化活性 |
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| Outline of Final Research Achievements |
Nascent polypeptide chains must fold into a unique 3D structure to exert their biological activity. This folding reaction, which is generally coupled with oxidative formation of disulfide bonds between cysteine residues, is controlled by an oxidoreductase, protein disulfide isomerase (PDI). However, the thiol groups existing in the redox active center of PDI are occasionally modified by a reactive oxygen (or nitrogen) species, resulting in the decrease in the enzymatic activity of PDI and thus generation of misfolded proteins, which are responsible for several neurodegenerative diseases. To prevent the generation of misfolded form, synthesis of novel cyclic diselenide compounds, which include three catalytic activities, i.e., (1) anti-oxidative ability, (2) reactivating ability for the deactivated PDI, and (3) promoting ability for protein folding, was conducted during this research term.
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| Academic Significance and Societal Importance of the Research Achievements |
超高齢化が進む我が国では、タンパク質の異常な構造変化に起因するアルツハイマー病などの神経変性病の患者数が増加し続けている。本研究は、そのような望ましくないタンパク質への構造変化を抑制、あるいは正常なタンパク質構造の復元を補助する試薬開発に関わるものである。合成に成功したいくつかの化合物について、これらの薬理効果を示唆するデータが得られており、今後の新薬開発に有益な指針を与えるものと考えられる。
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