Ligand-Directed Selective Protein Modification Based on Local Single- Electron-Transfer Catalysis

2014 Fiscal Year Final Research Report

• Project/Area Number: 25810104
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Bio-related chemistry
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: SATO Shinichi 東京工業大学, 資源化学研究所, 助教 (20633134)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: タンパク質化学修飾 / ケミカルラベリング / チロシン残基修飾 / タンパク質機能化 / 標的タンパク質 / 光触媒 / Ru(ｂｐｙ)3 / 一電子移動反応

Outline of Final Research Achievements

The chemical modification of proteins with synthetic probes is an important technique in chemical biology, protein-based therapy, and material science. It is an essential tool for the development of antibody-drug conjugates and protein-based drug delivery agents. Furthermore, The target-protein-selective chemical modification with small-molecule probes has received much interest as a powerful method for the study of individual proteins in their native environments.
We developed tyrosine-selective bioconjugation reaction using single-electron-transfer (SET) reaction. We found tyrosine modification reaction using a Ru(bpy)3 photocatalyst as a SET catalyst. N’-acetyl-N,N-dimethyl-1,4-phenylenediamine was found to be a suitable tyrosine modifier under the reaction condition with Ru(bpy)3 and visible light irradiation even in mild pH conditions (pH 6.0-7.4).
The target-selective protein modification was achieved using a ligand-conjugated Ru(bpy)3.

Free Research Field

ケミカルバイオロジー