Development of fluorescent probes to investigate copper metabolism and pathological dysfunction based on copper

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07035
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
• Research Institution: Kobe Pharmaceutical University
• Principal Investigator: Okuda Kensuke 神戸薬科大学, 薬学部, 教授 (00311796)
• Co-Investigator(Kenkyū-buntansha): 高木 晃 神戸薬科大学, 薬学部, 助教 (00758980)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 銅 / 亜鉛 / イメージング / 蛍光プローブ / シグナル増幅 / 代謝 / 病態 / 還元的環境

Outline of Final Research Achievements

Recently, the behavior of zinc and copper ions in various physiological and pathological conditions has attracted much attention. Various fluorescent probes have been developed as tools to analyze the roles of these ions in living systems. However, most of these probes are "coordination-type" fluorescent probes based on host-guest interactions, therefore their sensitivity is greatly reduced in the intracellular environment. In this study, we designed and developed "reaction-type" fluorescent probes based on a mechanism in which the fluorescent signal is enhanced by the reaction of target ions with multiple probe molecules by catalytic turnover. We succeeded in detecting intracellular zinc and copper at low concentrations, which cannot be detected by existing fluorescent probes, by using our "reaction-type" fluorescent probes.

Free Research Field

医薬化学、ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

様々な生態・病態における関与が知られる亜鉛や銅の機能解明において生体での挙動解析は必須であり、解析ツールの一つとしてこれら亜鉛や銅を非侵襲的にリアルタイムで解析可能な蛍光プローブが多数報告されている。本研究で創製した「反応型」蛍光プローブは既存の蛍光プローブよりも低濃度の細胞内亜鉛および銅を蛍光検出することができる。そこで、これまでに考えられているよりもさらに低い濃度で作用する亜鉛や銅の生体内機能を解析する上で、感度の面で有利な「反応型」の蛍光プローブは有力な解析ツールとなりうる。