2022 Fiscal Year Final Research Report
Screening for small molecule compounds that inhibit the biosynthesis of a specific cell-surface protein
| Project/Area Number |
20K21262
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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 38:Agricultural chemistry and related fields
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2020-07-30 – 2023-03-31
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| Keywords | 分泌タンパク質 / ジスルフィド結合 / 哺乳動物 / 小胞体 / 物質生産 / 低分子化合物 |
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| Outline of Final Research Achievements |
Some human cell surface proteins can cause disease. Antibodies that bind to these proteins and inhibit their functions have been developed as medicines. However, they are extremely expensive because of their high production costs. To solve the problem, here we have developed in cell assays to screen small molecule compounds that specifically inhibit the biosynthesis of the disease-causing human cell surface proteins. Our pilot screen allowed us to obtain information that will facilitate the future large scale screen of these molecules. Furthermore, the new assays enabled us to elucidate the molecular function of an ER membrane protein, whose genetic variations can lead to sever hypertriglyceridemia. These findings reveal the usefulness of our assay system for both applied and basic sciences.
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| Free Research Field |
応用生物化学
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| Academic Significance and Societal Importance of the Research Achievements |
疾病の原因になるヒト細胞表層タンパク質に結合し不活化する抗体は治療薬として有用だが、調製に多大なコストを要する。本研究では、抗体医薬に代わる廉価な低分子化合物を得るための第一歩として、疾病の原因となる細胞表層タンパク質の生合成を特異的に阻害する薬剤を探索するための系の構築を進めた。小規模の探索およびその後の解析から、実験系の効率化と、実験系の特質の解明に成功した。これは、今後の大規模探索に向けて大きな進展である。更に、作成した実験系を使って、変異によって脂質異常症を引き起こすタンパク質の分子機能の解明に役立つ知見を得た。よって、作成した実験系は基礎と応用の両面から有用であることが判明した。
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