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Updated: Jun 30, 2026

Harnessing the Bioorthogonal Inverse Electron Demand Diels-Alder Cycloaddition for Pretargeted PET Imaging
Published on: February 3, 2015
Tetrazine ligation: fast bioconjugation based on inverse-electron-demand Diels-Alder reactivity
Melissa L Blackman1, Maksim Royzen, Joseph M Fox
1Brown Laboratories, Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, USA.
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.
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