The Tetrazine Ligation: Fast Bioconjugation based on Inverse-electron-demand Diels-Alder Reactivity

By Melissa L. Blackman, M. Royzen, J. Fox. Journal of the American Chemical Society, 2008

1,373 citations recorded by the source corpus.

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 in cell lysate. The rate of the ligation between trans-cyclooctene and 3,6-di-(2-pyridyl)-s-tetrazine is very rapid (k2 2000 M−1s−1). This fast reactivity enables protein modification at low concentration.

Subfields: Molecular Biology, Organic Chemistry, Radiology, Nuclear Medicine and Imaging

View Paper: https://www.semanticscholar.org/paper/48a16bdbe4635f32c4eac8231c2bc782a5618a70

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In Molecular Biology

In Organic Chemistry

In Radiology, Nuclear Medicine and Imaging

Citations in the corpus

Noninvasive imaging of immune responses (2015, positive): “The TCO – tetrazine reaction is the fastest known bioorthogonal reaction to date, with an estimated second-order rate constant of 210 – 26,000 M -1 · s − 1 (27 – 29).”
Click Chemistry in Complex Mixtures: Bioorthogonal Bioconjugation (2014, background): “Strain-promoted alkynenitrone cycloaddition (SPANC) reactions demonstrate rate constants up to 60 M−1s−1 (McKay et al., 2012; McKay et al., 2010; Ning et al., 2010), and have been used for Nterminal peptide modification (Ning et al., 2010), direct protein labeling, and pre-targeted labeling of ligan”