Development of lipid antigen recognition protein ligands modulating cytokine balance in immune system
| Project/Area Number |
16K16638
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biomolecular chemistry
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| Research Institution | Kyoto University (2017-2018)
Keio University (2016) |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | サイトカインバランス / 糖脂質 / NKT細胞 / CD1d / 免疫調節 / 分子動力学計算 / 糖脂質リガンド / ケミカルバイオロジー / 有機合成化学 / 生物有機化学 |
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| Outline of Final Research Achievements |
We focused on CD1d protein involved in activation of NKT cells, and developed novel potent and selective CD1d glycolipid ligands that can modulate cytokine balance in immune system. The glycolipid derivatives containing various functional groups in their acyl chain parts were designed, synthesized and evaluated to identify a number of selective ligands. The binding mode analysis between the functional groups of lipid ligands and CD1d were also performed by using molecular dynamics simulation.
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| Academic Significance and Societal Importance of the Research Achievements |
免疫系におけるサイトカインバランスの制御は、創薬研究などにおいて重要な課題である。本研究では、NKT細胞を活性化するCD1dリガンドの構造展開によって、強力かつ選択的なサイトカイン誘導活性を有するリガンドの創製に成功した。本研究で見出した選択的リガンドは、サイトカインバイアス解析のツールとして関連分野に大きな進展をもたらすとともに、自己免疫疾患等に対する治療薬シーズとしての展開が期待される。
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Report
(4 results)
Research Products
(58 results)
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[Journal Article] Structure-activity relationship studies of Bz amide-containing α-GalCer derivatives as natural killer T cell modulators2019
Author(s)
Kishi, J., Inuki, S., Hirata, N., Kashiwabara, E., Yoshidome, D., Ichihara, O., Fujimoto, Y.
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Journal Title
Bioorg. Med. Chem. Lett.
Volume: 29
Issue: 8
Pages: 970-973
DOI
Related Report
Peer Reviewed
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[Journal Article] Potent Th2 Cytokine-Bias of Natural Killer T Cell by CD1d Glycolipid Ligands Based on “Anchoring Effect” of Polar Groups in Their Lipid Component.2018
Author(s)
Inuki, S., Kashiwabara, E., Hirata, N., Kishi, J., Nabika, E., Fujimoto, Y.
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Journal Title
Angew. Chem. Int. Ed.
Volume: 57
Issue: 31
Pages: 9655-9659
DOI
Related Report
Peer Reviewed
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[Journal Article] Isolated Polar Amino Acid Residues Modulate Lipid Binding in the Large Hydrophobic Cavity of CD1d.2016
Author(s)
Inuki, S., Aiba, T., Hirata, N., Ichihara, O., Yoshidome, D., Kita, S., Maenaka, K., Fukase, K., Fujimoto, Y.
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Journal Title
ACS Chem. Biol.
Volume: 11
Issue: 11
Pages: 3132-3139
DOI
Related Report
Peer Reviewed
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[Journal Article] Discovery of a Novel Scaffold as an Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Based on the Pyrrolopiperazinone Alkaloid, Longamide B.2016
Author(s)
Shiokawa, Z., Kashiwabara, E., Yoshidome, D., Fukase, K., Inuki, S., Fujimoto, Y.
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Journal Title
ChemMedChem
Volume: 11
Issue: 24
Pages: 2682-2689
DOI
Related Report
Peer Reviewed
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