Bioorthogonal Tetrazine Carbamate Cleavage by Highly Reactive trans-Cyclooctene
| Autor: | Jeremy Wu, Henk M. Janssen, Marc S. Robillard, Wolter ten Hoeve, Raffaella Rossin, Ivo A. W. Filot, Freek J. M. Hoeben, Tong Zhu, Ron M. Versteegen, Arthur H. A. M. van Onzen, Peter J. Hudson |
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| Přispěvatelé: | Macromolecular and Organic Chemistry, Inorganic Materials & Catalysis, EAISI Foundational |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Allylic rearrangement
General Chemistry 010402 general chemistry 01 natural sciences Biochemistry Combinatorial chemistry Tautomer Catalysis Cycloaddition 0104 chemical sciences Tetrazine chemistry.chemical_compound Elimination reaction Colloid and Surface Chemistry chemistry Reagent Click chemistry Bioorthogonal chemistry |
| Zdroj: | Journal of the American Chemical Society, 142(25), 10955-10963. American Chemical Society |
| ISSN: | 0002-7863 |
| Popis: | The high reaction rate of the 'click-to-release' reaction between allylic substituted trans-cyclooctene and tetrazine has enabled exceptional control over chemical and biological processes. Here we report the development of a new bioorthogonal cleavage reaction based on trans-cyclooctene and tetrazine with up to 3 orders of magnitude higher reactivity compared to the parent reaction, and 4 to 6 orders higher than other cleavage reactions. In this new pyridazine elimination mechanism, wherein the roles a reversed, a trans-cyclooctene activator reacts with a tetrazine that is substituted with a methylene-linked carbamate, leading to an 1,4-elimination of the carbamate and liberation of an amine. Through a series of mechanistic studies, we identified the 2,5-dihydropyridazine tautomer as the releasing species and found factors that govern its formation and subsequent fragmentation. The bioorthogonal utility was demonstrated by the selective cleavage of a tetrazine-linked antibody-drug conjugate by trans-cyclooctenes, affording efficient drug liberation in plasma and cell culture. Finally, the parent and the new reaction were compared at low concentration, showing that the use of a highly reactive trans-cyclooctene as activator leads to a complete reaction with antibody-drug conjugate in seconds vs. hours for the parent system. We believe that this new reaction may allow markedly reduced click-to-release reagent doses in vitro and in vivo and could expand the application scope to conditions wherein the trans-cyclooctene has limited stability. |
| Databáze: | OpenAIRE |
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