2022 Fiscal Year Final Research Report
Development of chemical tools to elucidate the molecular basis of T cell responses
| Project/Area Number |
20K06938
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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 47010:Pharmaceutical chemistry and drug development sciences-related
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 構造展開 / 医薬品探索 / ケミカルツール / 免疫応答 / T細胞 |
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| Outline of Final Research Achievements |
In this study, we explored MR1 and CD1a ligands that regulate the function of mucosa-associated invariant T (MAIT) cells and CD1a-restricted T cells involved in various diseases. A high-throughput screening system was established and compound screening was conducted. We synthesized various derivatives of identified hit compounds and analyzed their interaction with MR1 using docking simulations. In terms of CD1a ligands, we developed an evaluation system for ligand discovery and performed structure-activity relationship studies on lipopeptides derived from microorganisms to identify key structures responsible for the regulation of activity.
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| Free Research Field |
生物有機化学
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| Academic Significance and Societal Importance of the Research Achievements |
MAIT細胞やCD1a拘束性T細胞は、感染防御に加えて、がんや自己免疫疾患など様々な疾患に関与するため、その機能を制御するリガンドの開発は重要な研究課題である。本研究では、MAIT細胞やCD1a拘束性T細胞を制御するリガンドの探索のために、ハイスループットスクリーニング系の開発と、有機合成化学的アプローチによる構造展開を実施した。本研究で見出した新たなリガンドは、T細胞の機能を解析するためのケミカルツール、ワクチンアジュバントや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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