Modular Enzyme‐ and Light‐Based Activation of Cyclopropene–Tetrazine Ligation. (30th July 2019)

• Record Type: Journal Article
• Authors: Jiang, Ting; Kumar, Pratik; Huang, Wei; Kao, Wei‐Siang; Thompson, Adrian O.; Camarda, Frank M.; Laughlin, Scott T.
• Is Part Of: Chembiochem. Volume 20:Number 17(2019)
• Page Start: 2222
• Page End: 2226
• Publication Date: 2019-07-30
• Subjects: bioorthogonal chemistry -- protecting groups -- cyclopropene -- reductases -- tetrazines; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201900137
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: We describe a modular activation strategy for cyclopropene–tetrazine ligation. This activation strategy uses chemically diverse enzyme‐ or photolabile protecting groups as cyclopropene reactivity cages. The linkages between the caging groups and cyclopropene are through carbamates, thus permitting the application of diverse cages to allow bioorthogonal reactivity by administering enzymes or light. Abstract : Bulky cyclopropene "reactivity cages" suppress the reaction of s‐tetrazines and an amine‐bearing spirocyclic cyclopropene. These cages are modular, thus making it possible to integrate off‐the‐shelf cleavable protecting groups that can be removed by enzymes or light. We explore nitroreductase‐ and light‐labile caging groups that can be swapped in one step without altering the core cyclopropene scaffold.