タンパク質ケミカルラベリングにおける一電子移動反応の活用

抄録

The chemical labeling of proteins with synthetic small compound is an important technique in chemical biology. To achieve reliable bioconjugation, rapid reactions in aqueous under physiological pH and mild temperature are required. In the attempt to covalently label native proteins, various biorthogonal chemical reactions targeting not only nucleophilic amino acid residues such as lysine and cysteine, but also tyrosine, tryptophan, methionine, N- and C-terminal positions have been developed. The radical protein labeling reaction proceeds rapidly even in intracellular and physiological environment, and high reactivity of radical species enables local reaction control on the nanometer scale. In this paper, we introduce our recent studies on the labeling of protein tyrosine residues via single electron transfer initiated radical reaction, especially using ruthenium photocatalyst. We found the protein labeling at tyrosine residues with small compounds such as N’-acyl-N,N-phenylenediamine and 1-methyl-4-aryl-urazole under the reaction condition using ruthenium photocatalyst and visible light irradiation. Target-selective labeling using ligand-conjugated ruthenium photocatalysts, and target-selective-purification and labeling from protein mixture using catalyst-functionalized affinity beads were achieved.