| Project/Area Number |
23KJ0751
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| Research Category |
Grant-in-Aid for JSPS Fellows
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| Allocation Type | Multi-year Fund |
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| Section | 国内 |
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| Review Section |
Basic Section 38040:Bioorganic chemistry-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SHI YAOHONG 東京大学, 工学系研究科, 特別研究員(DC1)
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| Project Period (FY) |
2023-04-25 – 2026-03-31
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| Project Status |
Granted (Fiscal Year 2023)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2025: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2024: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2023: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | fatty acid / FFAR1 / FFAR4 / solid-phase synthesis / PUFA / GPCR |
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| Outline of Research at the Start |
Polyunsaturated fatty acids (PUFAs) are important regulators in the body to maintain regular physical function. However, the relationship between the PUFA structures and biological functions by receptors such as Free Fatty Acid Receptors (FFARs) is still under investigation. Because preparing PUFAs with diversified structures by chemical synthesis is highly tough, the PUFA-derived library will contribute to the biological studies of FFARs. In this research, I plan to construct the PUFA-derived library by solid-phase synthesis and investigate the agonistic activity on FFAR1 and FFAR4.
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| Outline of Annual Research Achievements |
In the past year, I have synthesized several PUFA analogs. These efforts have led to the successful synthesis of a series of innovative PUFA analogs with unique characteristics. According to the normal PUFAs, the following compounds were synthesized, most have no commercial sources: PUFAs with different double bond numbers from natural PUFAs as well as PUFAs with an odd number of carbon chains.
Furthering the pursuit of innovation, the synthesis expanded beyond the conventional PUFA structures, that is those of omega-3 or omega-6 fatty acids. In addition to these PUFAs, I also finished the synthesis of omega-2 and omega-1 PUFAs, which are rarely obtained from commercial suppliers. In the future, the biochemistry functions will be under discussion.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
This project has been progressing smoothly as planned.
It took approximately three months to optimize the current synthesis method and go through the standard synthesis process for all the PUFA analogs. After initially synthesizing several PUFAs, I encountered challenges with compound purification and purity determination, which required more effort than anticipated. However, after testing various experimental conditions, suitable methods for the post-processing steps were identified, and the target compounds were successfully obtained. Although these steps required additional time, they did not significantly hinder the overall progress.
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| Strategy for Future Research Activity |
The small PUFA-derived library has now been established with about 20 new PUFAs, most of which have no commercial sources.
In the future, the biochemical functions of these PUFAs will be initially studied.
The first assay method under consideration is the TGF-α shedding assay. By using this method, the activity of FFAR1 and FFAR4 will be screened in the synthesized PUFA-derived library. Based on the data obtained, appropriate analytical methods will be applied to assess different factors. Moreover, biased agonism will be investigated using traditional second-messenger assays, such as the cAMP accumulation assay or the Ca2+ mobilization assay, both of which offer high sensitivity.
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