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Modular Enzyme‐ and Light‐ Activatable Cyclopropene‐Tetrazine Ligation for Spatiotemporal Imaging of Biological Systems
Author(s) -
Jiang Ting,
Thompson Adrian,
Kumar Pratik,
Huang Wei,
Kao WeiSiang,
Laughlin Scott
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.00297
Subject(s) - cyclopropene , bioorthogonal chemistry , tetrazine , chemistry , biomolecule , enzyme , combinatorial chemistry , click chemistry , biochemistry , organic chemistry
Bioorthogonal chemistry has been optimized to provide a new scenario for imaging and perturbing the function of biomolecules like lipids, proteins and nucleic acids in cells and organisms. Generally, these optimizations have focused on developing new bioorthogonal pairs and improving reaction rates. Less well explored are reactions that permit control when and where the reactions occur. Here we report our newly developed 3‐N spirocyclopene, which can be modularly caged via diverse enzyme or photolabile protecting groups. These caged cyclopropenes are activated to react with tetrazine upon the removal of the bulky groups by uncaging enzymes or UV/visible illumination. Here we are glad to present synthesis of the novel cyclopropene scaffold, a panel of diverse photo‐caged and enzyme‐caged cyclopropenes, efficiency of uncaging, and analysis of reactivity between the caged and liberated cyclopropenes, and further the applications in diverse biological imaging. We expect this to be a powerful tool to control cyclopropene‐tetrazine biorthogonal ligation in living mammalian cells and organisms.