生体シグナルに応答して薬剤を放出するタンパク質被覆多孔質輸送体の開発
Project/Area Number |
20J14162
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Research Category |
Grant-in-Aid for JSPS Fellows
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Allocation Type | Single-year Grants |
Section | 国内 |
Review Section |
Basic Section 37010:Bio-related chemistry
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Research Institution | The University of Tokyo |
Principal Investigator |
趙 賢兒 東京大学, 工学系研究科, 特別研究員(PD)
|
Project Period (FY) |
2020-04-24 – 2022-03-31
|
Project Status |
Completed (Fiscal Year 2021)
|
Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2021: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2020: ¥1,100,000 (Direct Cost: ¥1,100,000)
|
Keywords | タンパク質 / Adhesives / Gating / Porous material / Protein / Guest release |
Outline of Research at the Start |
For realization of site-selective drug release, we design an adhesive covalent organic framework bearing multiple guanidinium ions for adhering proteins via salt-bridge formation. Through the structural transition of proteins in response to signals, site-selective drug release will be achieved.
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Outline of Annual Research Achievements |
Covalent organic frameworks (COFs) are promising candidate for drug carriers due to their large drug loading capacity and tunable functionality. However, site-selective drug release is required to make ideal drug carriers because leakage of drugs in non-target tissues leads to side effects. Therefore, in this study, we decided to use proteins as a gate to realize controlled drug release. Specifically, we design a bioadhesive COF (Glue-COF) bearing multiple guanidinium ion for immobilization of proteins. Since there are many types of proteins that undergoes a structural transition in response to biological signals, drug can be released at only target tissues. Calmodulin was chosen as a gate and controlled guest release through the conformational changes of calmodulin by calcium ions (Angew. Chem., Int. Ed. 2021, 60, 8932-8937, selected as a Hot Paper and Front Cover). These experimental results indicate the possibility that protein conformational changes can be used as gates for substance transportation. Many proteins are known to exhibit high binding efficiency to a specific molecule and cause a conformational change upon binding. This achievement is expected to have various applications such as the release of drugs in response to stimuli.
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Research Progress Status |
令和3年度が最終年度であるため、記入しない。
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Strategy for Future Research Activity |
令和3年度が最終年度であるため、記入しない。
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Report
(2 results)
Research Products
(2 results)