Abstract

Bioorthogonal ligations have found widespread use in biomedical research for site selective labeling of biomolecules in living systems. Discovering new reactions to expand the toolbox of bioorthogonal chemistry remains an important, yet challenging task as most reactions do not meet the stringent requirements of bioorthogonal reaction. As highly useful synthetic intermediates, ortho-quinone methides (oQMs) have been broadly utilized in the total synthesis of natural products but have rarely been applied to biological studies. The required harsh reaction condition to generate oQMs would be detrimental to the cell or living organism. In this highlight, we would like to describe our recent development of a new bioorthogonal ligation enabled by the “click” cycloaddition of ortho-quinolinone quinone methide (oQQM) and vinyl thioether (VT).

Keywords: Bioorthogonal ligation, ortho-quinone methide, vinyl thioether, chemical genetics, hetero-Diels-Alder cycloaddition, protein labeling.