| Project/Area Number |
20K05734
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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 | Sophia University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | エラスチン / desmosine / 環状ペプチド / LC-MS/MS / 質量分析 / デスモシン |
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| Outline of Research at the Start |
本研究では、当研究室で確立した有機合成法を基盤として、これまでの研究で推定した構造をもつエラスチン架橋部位の環状desmosineペプチドの化学合成を第一の目的とする。そして、合成した環状ペプチドと、天然由来のエラスチンの酵素分解物のLC-MS/MS解析および比較による、真の架橋部分構造の特定を最終目的とする。本研究の推進によって、長い間謎であったタンパク質エラスチンの架橋部位を含む三次元構造を世界で初めて解明する。
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| Outline of Final Research Achievements |
Stepwise Sonogashira and Negishi cross-coupling reactions of trisubstituted halopyridines and the corresponding amino acid wih protecting groups were carried out. Cyclic peptides were prepared via intramolecular condensation of the peptide with three alanines. Furthermore, we succeeded in constructing a second cyclic peptide consisting of two alanines and one serine by cross-coupling and condensation reactions.
By LC-MS/MS analysis of the synthesized cyclic desmosine peptide, we confirmed the retention time on LC and the fragment pattern of MS/MS in detail. As a result of the analysis, we were able to identify the structure of the peptide chain at the cross-linking portion of elastin.
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| Academic Significance and Societal Importance of the Research Achievements |
エラスチンの架橋ペプチド構造は長年謎であったため、本研究成果は学術的に意義深い。エラスチン分解ペプチドは、エラスチン分解に関わる疾患のバイオマーカーになり得るため、間接的に社会的意義も大きいと考えられる。
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