Chemical catalysis intervening to dynamism of biomacromolecular structures

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H00489
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 47:Pharmaceutical sciences and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Kanai Motomu 東京大学, 大学院薬学系研究科(薬学部), 教授 (20243264)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 触媒 / 光 / アミロイド / エピジェネティクス / アシル化 / ヒストン / 選択性

Outline of Final Research Achievements

Catalyst 1 was administered intravenously to 11-month-old Alzheimer's disease model mice and irradiated with 600 nm light 1 hour later. This procedure was repeated five times, and homogenate samples derived from the mouse hippocampus were evaluated by Western blotting. The results showed that Aβ dimer, produced by oxygenation was more strongly detected in the catalyst-treated and light-irradiated mice than in the catalyst-only mice, suggesting that Catalyst 1 promotes the photooxygenation of Aβ in the in vivo system. Catalytic photooxygenation reduced the amount of amyloid in the mouse brain by approximately 30%, indicating that this is due to enhanced degradation of oxygenated Aβ by microglial cells in the brain.

Free Research Field

有機合成化学

Academic Significance and Societal Importance of the Research Achievements

生体環境下で機能する化学触媒を創り出すことによって、生命のソフトウエアであるタンパク質翻訳後修飾を操作する基盤技術を創製し、この基盤技術を発展させて、通常は酵素が作り出している生体内化学秩序に対して化学触媒が介入することよって、概念的に新しい疾患治療のモダリティの創造へつなげることの概念実証を達成した。