| Project/Area Number |
19K07025
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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 47020:Pharmaceutical analytical chemistry and physicochemistry-related
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| Research Institution | Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology |
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Principal Investigator |
Tsumoto Hiroki 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 主任研究員 (00409385)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 質量分析 / 糖鎖 / 糖ペプチド / シアル酸 / 誘導体化 |
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| Outline of Research at the Start |
本研究では、独自に開発したシアル酸結合様式特異的アルキルアミド化法と質量分析法を組み合わせ、生物学的に異なる役割を果たしているシアル酸の結合様式まで区別することができる新規シアリル化糖鎖・糖ペプチド解析法の開発を目的とする。また、確立した分析手法をヒト血漿タンパク質の糖鎖・糖ペプチド解析に応用し、加齢に伴う糖鎖構造変化を明らかにする。
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| Outline of Final Research Achievements |
In this study, a method for analysis of sialyl glycans and glycopeptides using sialic acid linkage-specific derivatization was developed to discriminate between alpha2,3- and alpha2,6-sialic acid.
Semi-supercentenarians (SSCs, older than 105 years old) are a good example of human longevity, therefore physiological and biochemical analyses of SSCs can contribute to the understanding of healthy human aging. Using a combination of the developed method and LC-MS/MS, N-glycomics and N-glycoproteomics of plasma proteins obtained from SSCs and younger control groups were performed. As a result of LC-MS/MS analyses, 1676 N-glycopeptides from 91 proteins were identified and quantified. Among them, 366 N-glycopeptides were altered in SSCs compared to younger control groups. Furthermore, multivariate analysis identified 10 N-glycopeptides which were characteristic of SSCs. Most of the identified N-glycopeptides were derived from alpha1-acid glycoprotein 1.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究課題により開発された解析法を用いることにより，これまではLC分離や標準品入手が困難で解析不可能であった高分岐かつ高シアリル化糖鎖や糖ペプチドの結合様式の違いを容易に区別できる．それにより，より詳細なグライコミクスやグライコプロテオミクス研究の推進や疾患バイオマーカーの探索研究への貢献が期待できる．
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