Development of chemical biological tools to monitor and control pathologically important methyltransferase activites

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K14937
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Physical pharmacy
• Research Institution: The University of Tokyo
• Principal Investigator: Komatsu Toru 東京大学, 大学院薬学系研究科(薬学部), 助教 (40599172)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: ケミカルバイオロジー / 創薬化学 / 酵素

Outline of Final Research Achievements

Methyl transfer reactions play important roles in many biological phenomena, and the methylation cofactor S-adenosyl-L-methionine (SAM) serves as the important currency to govern those reactions inside cells. We have developed a fluorescent probe-based system to detect this important cofactor by fluorescence activation upon coupled reaction with protein L-isoaspartyl methyltransferase (PIMT). By carefully optimizing the molecular structures, the system was established as highly sensitive off-on or ratiometric type responsive platform that can quantify the cofactor as low as 20 nM within 10 min with mix-and-read platform. The system was applied (1) to detect the changes of cellular methylation potential at altered cellular conditions, and (2) to monitor general lysine methyltransferase reactions for inhibitor screening.

Free Research Field

ケミカルバイオロジー