Stable Pyrrole‐Linked Bioconjugates through Tetrazine‐Triggered Azanorbornadiene Fragmentation. (18th February 2020)

• Record Type: Journal Article
• Authors: Gil de Montes, Enrique; Istrate, Alena; Navo, Claudio D.; Jiménez‐Moreno, Ester; Hoyt, Emily A.; Corzana, Francisco; Robina, Inmaculada; Jiménez‐Osés, Gonzalo; Moreno‐Vargas, Antonio J.; Bernardes, Gonçalo J. L.
• Is Part Of: Angewandte Chemie. Volume 132:Number 15(2020)
• Page Start: 6255
• Page End: 6259
• Publication Date: 2020-02-18
• Subjects: Chemische Biologie -- Cycloadditionen -- Biokonjugation -- Heterocyclen -- Proteine; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201914529
• Languages: English
• ISSNs: 0044-8249

Abstract

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. Abstract : Stabiler Klick : Ein Azanorbornadienbromvinylsulfon‐Reagenz ermöglicht die ortsselektive Proteinmodifikation und liefert mit einem Tetrazin‐Partner stabile pyrrolgebundene Proteinkonjugate durch eine neue Bindungsspaltungsreaktion. Letztere verläuft über eine dreistufige Kaskade bestehend aus einer Diels‐Alder‐Cycloaddition mit inversem Elektronenbedarf und zwei Retro‐Diels‐Alder‐Reaktionen.