Accelerated Strain‐Promoted and Oxidation‐Controlled Cyclooctyne‐Quinone Cycloaddition for Cell Labeling

Abstract

Abstract We developed an accelerated strain‐promoted oxidation‐controlled cyclooctyne‐1,2‐quinone cycloaddition (SPOCQ) for protein modification. Here, dopaquinone was generated using potassium nitrosodisulfonate (PTN) in a reaction that is six orders of magnitude faster than the enzymatic one. The dopaquinone generated then reacts with bicyclononyne (BCN) derivatives in the bioconjugation. The PTN yields a single product with defined stereochemistry and temporally controlled conjugation with BCN. The feasibility of this bioconjugation was demonstrated with different proteins. Cell labeling was explored by conjugating annexin‐dibenzocyclooctyne‐PEG4‐fluor545 through the SPOCQ approach for the detection of apoptosis in HeLa cells.