| 研究課題/領域番号 |
23KJ0751
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| 研究機関 | 東京大学 |
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研究代表者 |
SHI YAOHONG 東京大学, 工学系研究科, 特別研究員(DC1)
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| 研究期間 (年度) |
2023-04-25 – 2026-03-31
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| キーワード | fatty acid / FFAR1 / FFAR4 / solid-phase synthesis / PUFA / GPCR |
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| 研究実績の概要 |
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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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
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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| 今後の研究の推進方策 |
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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| 次年度使用額が生じた理由 |
In the coming year, most of the funds will be allocated to purchasing reagents for biological experiments. With the majority of the synthesis now complete, I will shift my focus to studying the biochemical properties of the compounds. For this purpose, I will purchase various cell-related reagents and kits, which are more expensive than the synthesis reagents. Additionally, I will conduct the re-synthesis of PUFA analogs for which the current quantities are insufficient.
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