'Organisation for Economic Co-Operation and Development (OECD)'
Doi
Abstract
We have developed an azanorbornadiene bromovinyl
sulfone reagent that allows cysteine-selective bioconjugation.
Subsequent reaction with dipyridyl tetrazine led to bond-cleavage and
formation of a pyrrole-linked conjugate. The latter involves ligation of
the tetrazine to the azanorbornadiene-tagged protein through inverse
electron demand Diels–Alder cycloaddition with subsequent double
retro-Diels–Alder reactions to form a stable pyrrole linkage. The
sequence of site-selective bioconjugation followed by bioorthogonal
bond-cleavage was efficiently employed for the labelling of three
different proteins. This method benefits from easy preparation of
these reagents, selectivity for cysteine, and stability after reaction with
a commercial tetrazine, which lends it to the routine preparation of
protein conjugates for chemical biology studies
