Development of fluorescent probes with AND-logic gate response for HYPOXIA

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23816
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0801:Pharmaceutical sciences and related fields
• Research Institution: Kobe Pharmaceutical University
• Principal Investigator: Takashima Ippei 神戸薬科大学, 薬学部, 特任助教 (50769742)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: アンドロジック / 蛍光プローブ / 微量元素 / シグナル増強 / 低酸素環境 / がん微小環境

Outline of Final Research Achievements

Our research goal is the development of an AND logic gate targeting tumor-localized enzymes with a conventional hypoxia-sensitive molecule. In this project, we found that the enzyme we had planned to use for this system quickly degrades under physiological conditions, but a chemical modification of the enzyme overcame this issue. In addition, the enzyme substrate was also found to be unstable under physiological conditions, and the structure optimization efforts is underway. Through these optimization studies, we fortuitously found functional molecules that react selectively with zinc. The molecules were further applied as fluorescent probes to give a bright fluorescent response by signal amplification. These studies are also in progress and a part of results has been published in an international journal.

Free Research Field

生物有機化学

Academic Significance and Societal Importance of the Research Achievements

研究に用いる酵素の安定性を増す化学修飾方法を開発することでケミカルバイオロジー研究での新たなツールとなることが期待される。また本研究では、偶然に亜鉛に対するシグナル増強型の蛍光プローブを創製した。従来のプローブ分子に比べて高感度であり、生体中での微量の亜鉛を蛍光解析するのに優れた機能を持つ。また本研究概念は他の微量元素や生体内分子の検出に拡張可能であると思われ、蛍光プローブの開発における新たな分子設計指針としても有効であることが期待される。