2019/09/02 by Susanne V. Mayer, Anton Murnauer, Marie‐Kristin von Wrisberg +2 · 1 voice · 1 citation
Chemistry · Biochemistry, Genetics and Molecular Biology · Materials Science · #Click Chemistry and Applications #Chemical Synthesis and Analysis #Photochromic and Fluorescence Chemistry
paper · pdf · doi:10.1002/anie.201908209
openalex publication_date 2019/09/02 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
Inverse electron-demand Diels-Alder cycloadditions (iEDDAC) between tetrazines and strained alkenes/alkynes have emerged as essential tools for studying and manipulating biomolecules. A light-triggered version of iEDDAC (photo-iEDDAC) is presented that confers spatio-temporal control to bioorthogonal labeling in vitro and in cellulo. A cyclopropenone-caged dibenzoannulated bicyclo[6.1.0]nonyne probe (photo-DMBO) was designed that is unreactive towards tetrazines before light-activation, but engages in iEDDAC after irradiation at 365 nm. Aminoacyl tRNA synthetase/tRNA pairs were discovered for efficient site-specific incorporation of tetrazine-containing amino acids into proteins in living cells. In situ light activation of photo-DMBO conjugates allows labeling of tetrazine-modified proteins in living E. coli. This allows proteins in living cells to be modified in a spatio-temporally controlled manner and may be extended to photo-induced and site-specific protein labeling in animals.