2023 Fiscal Year Final Research Report
Study of the interaction between fibroblast growth factor FGF5 and its receptor and the inhibitory mechanism of aptamer
| Project/Area Number |
20K06529
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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 43020:Structural biochemistry-related
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| Research Institution | Chiba Institute of Technology |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
堀内 正隆 北海道医療大学, 薬学部, 准教授 (90322825)
杉山 成 高知大学, 教育研究部自然科学系理工学部門, 教授 (90615428)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Keywords | アプタマー / 線維芽細胞増殖因子 / 構造解析 / 物理化学的解析 / FGF |
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| Outline of Final Research Achievements |
We successfully obtained aptamers that bind to the fibroblast growth factor 5 (FGF5) using Systematic Evolution of Ligands by EXponential enrichment (SELEX) method and find that the aptamer specifically and tightly binds to FGF5. To reveal the interaction between FGF5 and aptamer at the atomic coordinate level, we synthesized deletion mutants. As a result, we succeeded in shortening the aptamer to 42 residues and confirmed that it retained FGF5 binding activity. NMR analysis of the mutant revealed that the aptamer has two stem-loop structures and a multi-branched loop. We also established a method to obtain aptamers more efficiently than conventional methods.
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| Free Research Field |
構造生物学
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| Academic Significance and Societal Importance of the Research Achievements |
アプタマーとよばれる核酸は，標的タンパク質に特異的に結合し，その機能を阻害することから，医薬品としての開発が行われている．アプタマー医薬品は，低分子製剤のように化学合成でき，抗体医薬品のように特異性が高いことから副作用が少ない次世代型分子標的薬として注目されている．本研究では，脱毛および血管新生に関わるFGF5タンパク質に結合するアプタマーの短鎖化に成功した．また，効率よくアプタマーを取得する方法を確立した．今後，アプタマーとFGF5の相互作用機序が明らかになれば，さらに効率よくアプタマー医薬品を開発できるようになることが期待される．
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