Study for molecules initiated lipid related disease biomarkers
| Project/Area Number |
17K19188
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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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| Research Field |
Biomolecular chemistry and related fields
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| Research Institution | Hokkaido University |
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Principal Investigator |
Monde Kenji 北海道大学, 先端生命科学研究院, 教授 (40210207)
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| Co-Investigator(Kenkyū-buntansha) |
村井 勇太 北海道大学, 先端生命科学研究院, 助教 (20707038)
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| Project Period (FY) |
2017-06-30 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | バイオマーカー / スフィンゴシン / セラミド / 異常取り込み / ライブラリー |
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| Outline of Final Research Achievements |
L-serine, the head part of a sphingosine, is incorporated by serine palmitoyl transferase (SPT）, coupled with a palmitoyl CoA in the first stage of its biosynthesis and converted into ceramides. Recently, it has been suggested that not only L-serine but also other amino acids may be incorporated into this biosynthetic system, and its association with lipid-related diseases has been trend. We have been succeeded in synthesizing sphingosines having phenylalanine, alanine, tryptophan, leucine, cysteine, and threonine in its head part for the purpose of providing authentic standard samples in a mass spectrometric analysis. We also constructed a unique ceramide library by binding some of these to fatty acids. It was found that some of them showed inhibitory activity of sphingomyelin synthase.
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| Academic Significance and Societal Importance of the Research Achievements |
スフィンゴ脂質は、動物、植物、バクテリア等ほとんどすべての生物にあまねく広く存在する。細胞膜の構成成分であると同時に、情報伝達、皮膚バリア機能等に重要な役割を果たしている。その基本構造であるスフィンゴシン骨格は、セリンとパルミトイルCoAからセリンパルミトイル転移酵素によって生合成される。近年、その他のアミノ酸が取り込みの可能性と疾患との関連性が示唆されているが、原因物質検出のための標準化合物は、これまで化学合成されていない。本研究では、異常取り込みの結果、生合成される可能性がある物質の化学合成を世界で初めて化学合成することに成功した。これにより脂質関連疾患のバイオマーカー研究が推進される。
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Report
(4 results)
Research Products
(36 results)
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[Journal Article] Nrp1 is activated by kCer binding-induced structural rigidification of the a1a2 domain2020
Author(s)
Usuki S., Yasutake Y., Tamura N., Tamura T., Tanji K., Saitoh T., Murai Y., Mikami D., Yuyama K., Monde K., Mukai K., Igarashi Y.
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Journal Title
Related Report
Peer Reviewed
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[Journal Article] Structure-inspired design of a sphingolipid mimic sphingosine-1-phosphate receptor agonist from a naturally occurring sphingomyelin synthase inhibitor2018
Author(s)
M.M.M. Swamy, Y Murai, Y Ohno, K Jojima, A Kihara, S Mitsutake, Y Igarashi, J Yu, M Yao, Y Suga, M Anetai and K Monde
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Journal Title
Chem. Commun.
Volume: 54
Issue: 90
Pages: 12758-12761
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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