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Tetrazine Ligation: Fast Bioconjugation Based on Inverse-Electron-Demand Diels−Alder Reactivity

2008/09/18 by Melissa L. Blackman, Maksim Royzen, Joseph M. Fox · 44 citations
Chemistry · Biochemistry, Genetics and Molecular Biology · Medicine · #Click Chemistry and Applications #Chemical Synthesis and Analysis #Monoclonal and Polyclonal Antibodies Research

paper · doi:10.1021/ja8053805

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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