Stable Pyrrole‐Linked Bioconjugates through Tetrazine‐Triggered Azanorbornadiene Fragmentation |
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Authors: | Enrique Gil de Montes,Alena Istrate,Claudio D. Navo,Ester Jim nez‐Moreno,Emily A. Hoyt,Francisco Corzana,Inmaculada Robina,Gonzalo Jim nez‐Os s,Antonio J. Moreno‐Vargas,Gon alo J. L. Bernardes |
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Affiliation: | Enrique Gil de Montes,Alena Istrate,Claudio D. Navo,Ester Jiménez‐Moreno,Emily A. Hoyt,Francisco Corzana,Inmaculada Robina,Gonzalo Jiménez‐Osés,Antonio J. Moreno‐Vargas,Gonçalo J. L. Bernardes |
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Abstract: | An azanorbornadiene bromovinyl sulfone reagent for cysteine‐selective bioconjugation has been developed. Subsequent reaction with dipyridyl tetrazine leads 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 has potential for the routine preparation of protein conjugates for chemical biology studies. |
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Keywords: | chemical biology cycloaddition bioconjugation heterocycles proteins |
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