Discovery of removable inhibitors targeting proteases
| Project/Area Number |
18K05344
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 37020:Chemistry and chemical methodology of biomolecules-related
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| Research Institution | Kobe Gakuin University |
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Principal Investigator |
Hidaka Koushi 神戸学院大学, 薬学部, 講師 (30445960)
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| Co-Investigator(Kenkyū-buntansha) |
津田 裕子 神戸学院大学, 薬学部, 教授 (10098478)
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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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | プロテアーゼ / 酵素活性 / リムーバブル阻害剤 / ビオチン / ストレプトアビジン / トリプシン / アミロイドベータ / HIVプロテアーゼ |
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| Outline of Final Research Achievements |
Inhibitors are widely used as tools for proteolytic enzyme functions and as therapeutic agents for various diseases. However, once bound, the inhibitor cannot be removed without protein denaturation or macro dilution, making it difficult to regain the enzymatic activity of the suppressed protease. In this research project, we created a "removable inhibitor" that freely controls enzyme activity by direct conjugation of biotin to various inhibitors targeting HIV protease, cathepsin D, and trypsin. Furthermore, we have obtained results that have led to the development of breakthrough diagnostic agents for HIV and cancer that combine removable inhibitors with affinity purification, and the development of protease drugs that degrade aggregated peptide.
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| Academic Significance and Societal Importance of the Research Achievements |
プロテアーゼを活性状態のまま阻害剤を取り除いて酵素活性を回復することができれば、それは真に制御すると言え、酵素活性を自在に調節できる。しかしながら、そのような手段はないのが現状である。本研究成果の「リムーバブル阻害剤」はその課題が解決できる。異なる２つのタンパク質相互作用を競合させて阻害剤を取り除く手法は報告はなく世界的にもユニークである。本成果のリムーバブル阻害剤は、自己消化が問題となるプロテアーゼの室温での保存、病気の解明につながる糖や脂質の修飾を受けた天然のプロテアーゼの酵素活性の解析、更に、疾患の原因となるタンパク質を分解するプロテアーゼ医薬品の新たな道を切り開くものである。
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Report
(4 results)
Research Products
(18 results)
