2022 Fiscal Year Final Research Report
Bottom-up approach to elucidate the molecular basis of immunomodulation by sialylglycans
| Project/Area Number |
20K05727
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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 37020:Chemistry and chemical methodology of biomolecules-related
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| Research Institution | Osaka 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 | 糖鎖 / シアル酸 / 免疫 / 糖鎖合成 / 糖鎖編集 |
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| Outline of Final Research Achievements |
In this study, we elucidated the immune regulation mechanism by sialic acid-containing glycans through a bottom-up approach using synthetic glycans as probes. First, we synthesized a library of sialylglycans. The synthesized glycans were then employed for the analysis of their recognition mechanism by sialic acid recognition lectins, including Siglec, at the molecular level. Furthermore, we developed a system to present synthetic glycans on the cell surface, and analyzed the interaction between glycans and lectins using living cell system. Through this research, we have constructed the fundamental methodology for the synthesis of sialylglycans. In addition, we clarified the molecular basis of sialic acid recognition. We also pioneered an innovative method to elucidate the functions of cell surface glycans and developed a novel glycan-based immunoregulatory method.
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| Free Research Field |
ケミカルバイオロジー
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の特徴は，合成糖鎖を用いて，分子レベルでの糖鎖認識の解析，細胞膜上での機能解析を実施した点である．糖鎖機能の解析は，糖鎖生合成酵素のノックアウトなどの分子生物学的手法を中心に進められてきた．これらの研究と合成糖鎖を用いた化学的なアプローチをとる本研究は相補的で，分子レベルでの糖鎖機能解析が進み，糖質科学の発展に大きく貢献した．また，Siglecは免疫応答に関わることから，自己免疫疾患やアレルギーといった疾病，免疫療法の開発などと関連が深い．そのため，シアリル糖鎖とSiglecの相互作用解明は，創薬への展開も期待でき，波及効果も大きい．
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