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Tetrazine

About: Tetrazine is a research topic. Over the lifetime, 1519 publications have been published within this topic receiving 29055 citations.


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Journal ArticleDOI
TL;DR: A bioorthogonal reaction that proceeds with unusually fast reaction rates without need for catalysis: the cycloaddition of s-tetrazine and trans-cyclooctene derivatives, which enables protein modification at low concentration.
Abstract: Described is a bioorthogonal reaction that proceeds with unusually fast reaction rates without need for catalysis: the cycloaddition of s-tetrazine and trans-cyclooctene derivatives. The reactions tolerate a broad range of functionality and proceed in high yield in organic solvents, water, cell media, or cell lysate. The rate of the ligation between trans-cyclooctene and 3,6-di-(2-pyridyl)-s-tetrazine is very rapid (k2 2000 M−1 s−1). This fast reactivity enables protein modification at low concentration.

1,257 citations

Journal ArticleDOI
TL;DR: Tetrazines conjugated to a near-infrared fluorochrome selectively and rapidly label thepretargeted antibody in the presence of serum suggests that it may prove a useful strategy for in vivo pretargeted imaging under numerous modalities.

689 citations

Journal ArticleDOI
TL;DR: The recent efforts to design extremely rapid bioorthogonal coupling reactions between tetrazines and strained alkenes are discussed and recent success in using tetrazine reactions to label biomarkers on cells with magneto-fluorescent nanoparticles is described.
Abstract: Disease mechanisms are increasingly being resolved at the molecular level. Biomedical success at this scale creates synthetic opportunities for combining specifically designed orthogonal reactions in applications such as imaging, diagnostics, and therapy. For practical reasons, it would be helpful if bioorthogonal coupling reactions proceeded with extremely rapid kinetics (k > 103 M–1 s–1) and high specificity. Improving kinetics would minimize both the time and amount of labeling agent required to maintain high coupling yields. In this Account, we discuss our recent efforts to design extremely rapid bioorthogonal coupling reactions between tetrazines and strained alkenes.These selective reactions were first used to covalently couple conjugated tetrazine near-infrared-emitting fluorophores to dienophile-modifed extracellular proteins on living cancer cells. Confocal fluorescence microscopy demonstrated efficient and selective labeling, and control experiments showed minimal background fluorescence. Multis...

415 citations

Journal ArticleDOI
TL;DR: The use of inverse electron demand Diels-Alder cycloaddition between a serum stable 1,2,4,5 tetrazine and a highly strained trans-cyclooctene to covalently label live cells is shown to be fast and can be amplified by increasing the loading of dienophile on the antibody.
Abstract: There is considerable interest in the use of bioorthogonal covalent chemistry such as “click” chemistries to label small molecules located on live or fixed cells.[1] Such labeling has been used for the visualization of glycans, activity based protein profiling, site-specific tagging of proteins, detection of DNA and RNA synthesis, revealing the fate of small molecules in plants, and detection of post-translational modification in proteins.[2-4] Most reported applications rely on either the copper catalyzed azide-alkyne cycloaddition, which is limited to in vitro application due to the cytotoxicity of copper, or the elegant strain-promoted azide-alkyne cycloaddition, which permits live cell and in vivo application use but is hindered by relatively slow kinetics and often difficult synthesis of cyclooctyne derivatives.[4-5] New bioorthogonal reactions that do not require catalyst and show rapid kinetics are therefore of interest for different molecular imaging applications at the cellular level. In this report we demonstrate the use of inverse electron demand Diels-Alder cycloaddition between a serum stable 1,2,4,5 tetrazine and a highly strained trans-cyclooctene to covalently label live cells. This chemistry has been applied to the pretargeted labeling of Cetuximab (Erbitux) tagged epidermal growth factor receptor (EGFR) on A549 cancer cells. We find that the tetrazine cycloaddition to trans-cyclooctene labeled cells is fast and can be amplified by increasing the loading of dienophile on the antibody. This results in a highly sensitive targeting strategy that can be used to label proteins using nanomolar concentrations of a secondary agent for short durations of time.

362 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202360
2022164
202171
2020109
201975
201892