ArticleNature chemistry2022
Light-activated tetrazines enable precision live-cell bioorthogonal chemistry.
Article in Nature chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed.
- Bioorthogonal chemistry for deciphering lipid biology in living systems.RSC chemical biology · 2026Review
- Organelle-Resolved Tetrazine-trans-Cyclooctene Click Chemistry for Cargo Delivery and Release.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- Palladium-triggered bioorthogonal phenylalanine decaging.Nature chemistry · 2026Article
- Tumour-specific bioorthogonal synthesis of proteolysis-targeting chimeras and nanoparticles boosts T cell activity.Nature biomedical engineering · 2026Article
- Red light-responsive bioorthogonal chemistry enabled on-demand prodrug activation for cancer therapy.Acta pharmaceutica Sinica. B · 2026Article
- Solvatochromism and Click Reactivity of Yellow Tetrazines.Bioconjugate chemistry · 2026Article
- Toward Chromoselective Transformations in Biological Systems: Perspectives and Challenges.Angewandte Chemie (International ed. in English) · 2026Review
- Tetrazine-Enabled Peptide Macrocyclization and Bioorthogonal Cell Penetration Profiling.JACS Au · 2026Article
- Tetrazine Ligation in Living Systems: Beyond Fast Kinetics to Effective Bioorthogonality.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Review
- Achieving cell-type-specific bioorthogonal chemistry using enzyme-activated caged tetrazines.Nature chemical biology · 2026Article
- Engineering an immuno-nanoprodrug: Photo-controlled pyroptosis synergizing with acid-activatable immunometabolic blockade for potent cancer immunotherapy.Acta pharmaceutica Sinica. B · 2026Article
- Covalent Network Formation Rate Controls Depletion-Induced Supramolecular Assembly in Hybrid Double Network Hydrogels.Angewandte Chemie (International ed. in English) · 2026Article
- Tunable Cell Surface Proximity Labeling via Photocatalytic and Enzymatic Activation of Fast Bioorthogonal Chemistry.Journal of the American Chemical Society · 2026Article
- Beyond Self-Assembly: Bioorthogonal 'Click' Chemistry Strategies for Robust Electrochemical Interfaces in Wearable Biosensors.Biosensors · 2026Review
- Directed Evolution of Enzymes for Bioorthogonal Chemistry Using Acid Chloride Proximity Labeling.ACS central science · 2026Article
- A Noncovalent Click-to-Release Strategy to Control Bond Cleavage and Prodrug Activation.Angewandte Chemie (International ed. in English) · 2026Article
- Reactive oxygen species-activated bioorthogonal chemistry in living systems enabled by boronate-caged dihydrotetrazines.Nature communications · 2026Article
- Spatiotemporally controlled drug release via a click-release system utilizing mono-alkyl-hydroxylamine and cyclooctyne chemistry.Nature communications · 2026Article
- Photoactivation in Chemotherapeutic Compounds for Cancer Treatment: Opportunities Beyond Photodynamic Therapy.Bioinorganic chemistry and applications · 2026Review
- Control of Tetrazine Bioorthogonal Reactivity by Rotaxanation.Angewandte Chemie (International ed. in English) · 2025Article
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Authors and funding
4 authors.
Funding
Abstract
Bioorthogonal cycloaddition reactions between tetrazines and strained dienophiles are widely used for protein, lipid and glycan labelling because of their extremely rapid kinetics. However, controlling this chemistry in the presence of living mammalian cells with a high degree of spatial and temporal precision remains a challenge. Here we demonstrate a versatile approach to light-activated formation of tetrazines from photocaged dihydrotetrazines. Photouncaging, followed by spontaneous transformation to reactive tetrazine, enables live-cell spatiotemporal control of rapid bioorthogonal cycloaddition with dienophiles such as trans-cyclooctenes. Photocaged dihydrotetrazines are stable in conditions that normally degrade tetrazines, enabling efficient early-stage incorporation of bioorthogonal handles into biomolecules such as peptides. Photocaged dihydrotetrazines allow the use of non-toxic light to trigger tetrazine ligations on living mammalian cells. By tagging reactive phospholipids with fluorophores, we demonstrate modification of HeLa cell membranes with single-cell spatial resolution. Finally, we show that photo-triggered therapy is possible by coupling tetrazine photoactivation with strategies that release prodrugs in response to tetrazine ligation.
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