Development of fluorescent probes highly sensitive to membrane potential and their design principles

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K05729
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 37030:Chemical biology-related
• Research Institution: Utsunomiya University
• Principal Investigator: Oba Toru 宇都宮大学, 工学部, 教授 (30291793)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 蛍光プローブ / 膜電位 / 神経細胞 / 超分子 / ケミカルバイオロジー

Outline of Final Research Achievements

To overcome psychiatric disorder or dementia, this study aims at developing highly sensitive voltage-sensitive fluorescent dyes for study and diagnosis of nerve cell networks. We found a new method to evaluate voltage-sensitivity of the dyes by utilizing micellar dipole potential. Exploration of the voltage-detecting part indicated that a quinoline-based dye with a dimethylaminophenylethynyl moiety as a promising structure. We successfully synthesized a new bodipy dye with this voltage-detecting part, and confirmed their voltage-sensitivity. We also obtained boron-containing amino-acid analogs that can be used to link the dyes to lipids or proteins.

Free Research Field

ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

①高感度な膜電位感受性蛍光色素の新たな分子設計指針を得ることができた。すなわち、電位検出部位と蛍光発色団を分離し、電子移動消光などにより速やかに励起エネルギーを散逸させることによって、感度と光安定性とを両立させることである。②この色素は神経細胞の診断の他にも、心筋のイオンチャネル標的薬のスクリーニングや、ミトコンドリア病の診断、ウイルスの侵入や放出に伴う細胞膜の変化の検出にも応用を期待できる。③新たに合成したホウ素化合物は、抗がん剤原料などにも応用できるだろう。