3-Bromotetrazine: labelling of macromolecules via monosubstituted bifunctional s-tetrazines

Schnell, Simon D.; Hoff, Lukas V.; Panchagnula, Advaita; Wurzenberger, Maximilian H.; Klapötke, Thomas M.; Sieber, Simon; Linden, Anthony and Gademann, Karl (2020): 3-Bromotetrazine: labelling of macromolecules via monosubstituted bifunctional s-tetrazines. In: Chemical Science, Vol. 11, No. 11: pp. 3042-3047

Abstract

We report the synthesis and first characterisation of the novel chemical probe 3-bromotetrazine and establish its reactivity towards nucleophiles. This led to the synthesis of several novel classes of 3-monosubstituted s-tetrazines. A remarkable functional group selectivity is observed and is utilised to site-selectively functionalise different complex molecules. The stability of 3-bromotetrazine under the reaction conditions facilitated the development of a protocol for protein functionalisation, which enabled a "minimal", bifunctional tetrazine unit as a bio-orthogonal handle for inverse electron demand Diels-Alder reactions. Additionally, a novel tetrazine-based chemical probe was developed and its application in the context of thiol-targeted natural product isolation and labelling of mammalian cells is demonstrated.

• Item Type: Journal article
• Faculties: Chemistry and Pharmacy > Department of Chemistry
• Subjects: 500 Science > 540 Chemistry
• ISSN: 2041-6520
• Language: English