ArticleJournal of the American Chemical Society2018
Unraveling Tetrazine-Triggered Bioorthogonal Elimination Enables Chemical Tools for Ultrafast Release and Universal Cleavage.
Article in Journal of the American Chemical Society, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
84 citing papers in PubMed.
- Organelle-Resolved Tetrazine-trans-Cyclooctene Click Chemistry for Cargo Delivery and Release.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- Red light-responsive bioorthogonal chemistry enabled on-demand prodrug activation for cancer therapy.Acta pharmaceutica Sinica. B · 2026Article
- Bioorthogonal Activation of Protein Function through a retro-Cope/Cope Elimination Cascade.Journal of the American Chemical Society · 2026Article
- Small-Molecule Activation of mRNA Translation by Click-to-Release Reaction in Cells.Angewandte Chemie (International ed. in English) · 2026Article
- Expanding the toolbox of bioorthogonal activation of photosensitizers for precise photodynamic therapy through transition metal-mediated deallylation.Materials today. Bio · 2026Article
- Click-to-Release Reactions for Tertiary Amines and Pyridines.Journal of the American Chemical Society · 2026Article
- Tetrazine-Inorganic chemistry frontiers · 2026Article
- Small-molecule control of CAR T cells.Nature reviews. Chemistry · 2025Review
- Multilayer Fluorescent Immunoassay for Early and Sensitive Dengue Virus Detection Using Host and Viral Biomarkers.Bioconjugate chemistry · 2025Article
- Article
- Temporal and spatial omics technologies for 4D profiling.Nature methods · 2025Review
- Click-Controlled Photo-Uncaging: Click-Assembly of Platinum-Based Photoactive Protecting Groups for Light-Triggered Bioactive Molecule Release.Journal of the American Chemical Society · 2025Article
- Prodrug Strategy for PROTACs: High Efficiency and Low Toxicity.ACS omega · 2025Review
- Click-Triggered Bioorthogonal Bond-Cleavage Reactions.Topics in current chemistry (Cham) · 2025Review
- Exploring β-catenin and TCF4 interaction in complex environments by means of novel biosensing platform focal molography.PloS one · 2025Article
- Ortho-functionalized pyridinyl-tetrazines break the inverse correlation between click reactivity and cleavage yields in click-to-release chemistry.Communications chemistry · 2024Article
- Scission-Enhanced Molecular Imaging (SEMI).Bioconjugate chemistry · 2024Article
- Engineering Pyrrolysine Systems for Genetic Code Expansion and Reprogramming.Chemical reviews · 2024Review
- Trans-cyclooctene-a Swiss army knife for bioorthogonal chemistry: exploring the synthesis, reactivity, and applications in biomedical breakthroughs.EJNMMI radiopharmacy and chemistry · 2024Review
- Advances in the Synthesis of Bioorthogonal Reagents: s-Tetrazines, 1,2,4-Triazines, Cyclooctynes, Heterocycloheptynes, and trans-Cyclooctenes.Topics in current chemistry (Cham) · 2024Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Recent developments in bond cleavage reactions have expanded the scope of bioorthogonal chemistry beyond click ligation and enabled new strategies for probe activation and therapeutic delivery. These applications, however, remain in their infancy, with further innovations needed to achieve the efficiency required for versatile and broadly useful tools in vivo. Among these chemistries, the tetrazine/ trans-cyclooctene click-to-release reaction has exemplary kinetics and adaptability but achieves only partial release and is incompletely understood, which has limited its application. Investigating the mechanistic features of this reaction's performance, we discovered profound pH sensitivity, exploited it with acid-functionalized tetrazines that both enhance and markedly accelerate release, and ultimately uncovered an unexpected dead-end isomer as the reason for poor release. Implementing facile methods to prevent formation of this dead end, we have achieved exceptional efficiency, with essentially complete release across the full scope of physiologic pH, potentiating drug-delivery strategies and expanding the dynamic range of bioorthogonal on/off control.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.