Synthesis and biofunctional elucidation of complex lipids involved in biological defense
Project/Area Number |
17H02207
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Biomolecular chemistry
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Research Institution | Keio University |
Principal Investigator |
Fujimoto Yukari 慶應義塾大学, 理工学部(矢上), 教授 (00362616)
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Co-Investigator(Kenkyū-buntansha) |
松丸 尊紀 慶應義塾大学, 理工学部(矢上), 助教 (90636549)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2019: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
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Keywords | 複合脂質 / 有機合成 / 免疫調節 / 自然免疫受容体 / 生体防御 / 有機化学 / 生物活性 / 生体分子化学 |
Outline of Final Research Achievements |
In this study, we established synthetic methods for immunostimulatory complex lipids involved in biological defense, and then evaluated the biological activities and the intermolecular interactions with the innate immune receptor/protein factors using the synthesized compounds as ligands. Among these analyses, we included the analysis of contribution of polar residue of lipid binding sites, which we have recently discovered, to binding stability. Based on the results, we also designed novel immunomodulatory compounds and molecular probes for further understanding of the innate immune system.
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Academic Significance and Societal Importance of the Research Achievements |
本研究では、生体防御機構に関わる環境中あるいは生体内の複合脂質分子について合成・解析を進め、まだ未知の部分の多い自然免疫-獲得免疫の連携・調節機構を含めた生体防御機構の解明のため、有機化学の強みを生かした活性分子設計、新規合成、および分子プローブを利用した解析手法を開発した。また、新規免疫制御性物質の創製についても行った。免疫機構の理解と制御に関わる鍵分子を武器に、人類の生命を脅かす感染症や癌、大きな社会問題ともなっているアレルギー疾患等に関する分子レベルでの理解を深めるために貢献出来たと考えている。
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Report
(4 results)
Research Products
(139 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] Synthetic analogs of an Entamoeba histolytica glycolipid designed to combat intracellular Leishmania infection.2017
Author(s)
Choy, S.L.; Bernin, H.; Aiba, T.; Bifeld, E.; Lender, S.C.; Muhlenpfordt, M.; Noll, J.; Eick, J.; Marggraff, C.; Niss, H.; Roldan, N.G.; Tanaka, S.; Kitamura, M.; Fukase, K.; Clos, J.; Tannich, E.; Fujimoto, Y.; Lotter, H.
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Journal Title
Sci. Rep.
Volume: 7
Issue: 1
Pages: 1-14
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Funiculosin variants and phosphorylated derivatives promote innate immune responses via the Toll-like receptor 4/myeloid differentiation factor-2 complex2017
Author(s)
Okamoto N, Mizote K, Honda H, Saeki A, Watanabe Y, Yamaguchi-Miyamoto T, Fukui R, Tanimura N, Motoi Y, Akashi-Takamura S, Kato T, Fujishita S, Kimura T, Ohto U, Shimizu T, Hirokawa T, Miyake K, Fukase K, Fujimoto Y, Nagai Y, Takatsu K
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Journal Title
Journal of Biological Chemistry
Volume: 292
Issue: 37
Pages: 15378-15394
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Presentation] Synthetic study of dragmacidin C2021
Author(s)
Shusuke Fujii, Shota Kawakami, Yohei Arai, Zenyu Shiokawa, Takanori Matsumaru, Shinsuke Inuki, Yukari Fujimoto
Organizer
The International Chemical Congress of Pacific Basin Societies 2021 (Pacifichem 2021)
Related Report
Int'l Joint Research
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[Presentation] Synthesis and immunomodulatory activities of glycoconjugates containing lyso-phosphatidyl inositol2018
Author(s)
Yukari Fujimoto, Toshihiko Aiba, Ryota Saito, Sae Suehara, Etsuko Nabika, Yohei Arai, Siew-Ling Choy, Hannah Bernin, Hannelore Lotter, Koichi Fukase, Shinsuke Inuki, and Takanori Matsumaru
Organizer
The 29th International Carbohydrate Symposium in 2018 (ICS 2018)
Related Report
Int'l Joint Research
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[Presentation] Glycolipids as activators of NKT cells; Synthesis and Immunomodulatory activities2017
Author(s)
Toshihiko Aiba, Natsumi Hirata, Emi Kashiwabara, Yohei Arai, Junichiro Kishi, Takanori Matsumaru, Siew-Ling Choy, Osamu Ichihara, Daisuke Yoshidome, Hannelore Lotter, Koichi Fukase, Shinsuke Inuki1, Yukari Fujimoto
Organizer
6th Gratama Workshop Groningen
Related Report
Int'l Joint Research / Invited
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