| Project/Area Number |
18K19278
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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 43:Biology at molecular to cellular levels, and related fields
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| Research Institution | Hokkaido 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 |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | HLA / 薬剤副作用 / 免役応答 / 薬剤過敏症 / タンパク質 / スクリーニング / 創薬 / 免疫応答 / 薬物副作用 / 蛋白質 / 免疫制御 / 物理化学解析 |
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| Outline of Final Research Achievements |
Using HLA-G, commonly exists in human, as an example, we focused on binding candidate drugs that can be predicted to be associated with disease, based on the results of the FDA-approved drug screening performed by a screening method using HLA proteins developed by ourselves. We then prepared a putative complex of HLA-G and binding candidate drug in vitro and performed mass spectroscopy. The analyzed result demonstrated the binding between the candidate drug and the HLA-G protein.
On the other hand, we focused the anti-HIV drug, abacavir, and the HLA-B * 57: 01 polymorphism, in which the binding of HLA and drugs associated with drug hypersensitivity and changes in the presented peptide pattern have been elucidated at the molecular level. When our screening method was applied to HLA-B*57:01 and abacavir, we can determine the binding of abacavir to HLA-B57, suggesting the possibility of developing into a universal and versatile method.
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| Academic Significance and Societal Importance of the Research Achievements |
HLA分子を介して薬剤副作用を誘発する薬物を見出すための本研究のアプローチは、従来のコホート研究と異なって全く新しい試みであり、これまで、早期発見・対処しか手の施しようがなかった薬剤過敏症症候群に対して有効な予防の指針を与えると期待できる。代表者等が構築したスクリーニング方法により、薬剤過敏症と関連するHLAと薬剤の結合等が既に明らかにされている抗HIV薬・アバカビルとHLA-B*57:01との結合が判定できたことや他のHLAにて複数の結合候補薬剤を判別できたことは非常に意義深い。本スクリーニング法を最適化し汎用性を高めることで、創薬における安全性評価に貢献し、幅広く波及する成果となりうる。
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