| Project/Area Number |
18K14350
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 37030:Chemical biology-related
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| Research Institution | Hokkaido University |
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Principal Investigator |
Murai Yuta 北海道大学, 先端生命科学研究院, 助教 (20707038)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 光アフィニティーラベル / ジアジリン / 芳香族求核置換反応 / マイゼンハイマー錯体 / ノシル基 / スフィンゴミエリン合成酵素 / 阻害剤 / マルチタグ / 芳香族求核反応 |
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| Outline of Final Research Achievements |
In existing photoaffinity labeling methods, there are some problems such as decreasing the original affinity of a ligand due to their bulkiness of the photoaffinity probe and complicated work within an analysis time. Therefore, innovative improvement of the photoaffinity labeling methodology as a simpler analysis tool for all researchers is required. In this study, I developed a novel photoaffinity probe possessing multi-tag exchangeable ability utilizing the characteristics of the nosyl chemistry. The developed photoaffinity probe improved the photolabeling efficiency to the target molecule, and can be exchanged for detection groups (fluorescent group or ion sensitizer) of the ligand by nucleophilic aromatic substituted reaction (SNAr). These advantages was able to overcome the previous problems and may contribute a large number of chamical biology research field.
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| Academic Significance and Societal Importance of the Research Achievements |
これまで解析が困難であった光アフィニティーラベル対象物（極微量なタンパク質）にも適用が可能であり、従来では数ヶ月以上要した解析期間を数週間程度に減らすことも可能であると期待される。これによってx線結晶構造解析やSTD-NMRで困難となっている対象の構造基盤創薬の代替法として活用でき、特に膜タンパク質などの創薬ターゲットとなる生体分子への応用が広がれば、その開発速度により一層拍車がかかると期待される。
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