Development of fluorescent probes for acrolein, a product of lipid peroxidation

• Project/Area Number: 17H06580
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Chemical biology
• Research Institution: The University of Tokyo
• Principal Investigator: Sasaki Eita 東京大学, 大学院農学生命科学研究科(農学部), 助教 (00803157)
• Project Period (FY): 2017-08-25 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 蛍光プローブ / アクロレイン / 脂質過酸化物 / ケミカルバイオロジー

Outline of Final Research Achievements

We designed and synthesized functional fluorescence probes whose spectroscopic properties are altered upon reaction with acrolein, a reactive aldehyde species produced in vivo. One of the designed probes possessing a 7-nitrobenzoxadiazole scaffold with aryl azide substituent reacted with acrolein. Since the reaction product showed substantially red-shifted absorbance spectrum, it is possible to excite only the product in the measurement of fluorescence to detect acrolein. However, these azide-based fluorescence probes were not very stable and converted to the corresponding amino compounds over time. Thus, we also investigated and designed another type of fluorescence probes by using Michael addition of a sulfhydryl group to acrolein.

Academic Significance and Societal Importance of the Research Achievements

本研究は、生細胞内でのアクロレインのイメージングを可能とする分子プローブの開発を行うものである。生体内で生じるアクロレインは、生活習慣病や癌、そして老化とも密接に関わる危険因子として注目されている。したがって、アクロレインの生成を高感度に検出・イメージングすることができれば、これらの疾病や加齢のメカニズム研究、予防、診断などの役に立つことが期待される。