Turning on bioorthogonal reactions catalytically

Abstract

To attach probes for imaging to biomolecules inside cells or organisms, chemists have developed so-called bioorthogonal reactions that don’t interfere with the biochemistry of the living things. Tetrazine ligation is the fastest of these bioorthogonal reactions, and its speed allows scientists to use small amounts of reagents to get the job done. A new catalytic form of this ligation could enable researchers to control the timing and location of the reaction inside cells or organisms by turning on the chemistry with either an enzyme or a pulse of light. Early bioorthogonal reactions were slow, so scientists had to introduce reagents at undesirably high concentrations to ensure the compounds could react before being cleared away by metabolic processes. Researchers developed faster reactions so they could use reagents at lower concentrations. Tetrazine ligation, which is now used widely in bioorthogonal chemistry, involves the cycloaddition of tetrazine with a trans-cyclooctene or another strained