Development of molecular probes for metabolic reaction analysis at specific environmental sites in vivo

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19193
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Biomolecular chemistry and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Nonaka Hiroshi 東京大学, 大学院工学系研究科(工学部), 講師 (80579269)
• Research Collaborator: SANDO SHINSUKE
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: 人工代謝物 / 分子プローブ

Outline of Final Research Achievements

In this study, we aimed to obtain the information about metabolic reactions in a specific environment high selectively. Hydrogen peroxide was selected as the disease-related environment in vivo, and gamma-glutamyl transpeptidase (GGT) was selected as the disease-related metabolic enzyme. We designed, synthesized, and evaluated a molecular probe BCGA that showed a signal under the condition that both of them were aligned. BCGA showed OFF/ON type fluorescence signal only in the coexistence condition of hydrogen peroxide and GGT, and no fluorescence was observed in the condition where either one did not exist. From these results, it has been confirmed that BCGA functions as an AND logic gate type probe.

Free Research Field

ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

本研究は、化学的な工夫を埋め込んだ人工的な代謝物を利用して、特定の環境での代謝反応を高選択的に得る手法の開発を目指した。生物内での特定の環境での代謝反応を解析できることは、特定代謝反応の理解・未知メカニズムの解明への貢献や、病気から起こる特定代謝異常を察知する早期診断・治療法選択への応用が期待される。本研究では、コンセプトモデルとして、過酸化水素とGGTという酵素が存在する条件で蛍光を発する分子センサーを提案した。