SCHEDULED MAINTENANCE
Chemical trigger-enabled bioconjugation reaction†
*a
Abstract
Development of conceptually novel and practically useful bioconjugation reactions has been an intense pursuit of chemical biology research. Herein, we report an unprecedented bioconjugation reaction that hinges on a chemical trigger-enabled inverse-electron-demand Diels–Alder (IEDDA) cycloaddition of trans-cycloheptene (TCH) with tetrazine. Unlike the conventional strain-promoted bioconjugation reactions that utilize built-in strained alkenes as reactants, the current one features a “trigger-release-conjugate” reaction model, in which a highly strained TCH species is released from a bench-stable bicyclic N-nitrosourea (BNU) derivative upon treatment with an external stimulus. It is noteworthy that the reactivity–stability balance of BNU derivatives could be tuned by manipulating their N-1 substituents. As a proof-of-concept case, this new chemical trigger-enabled IEDDA reaction has been applied to in vitro protein labeling and pretargeted cell imaging. This work opens a new avenue to utilize BNU derivatives as a new class of chemical reporters in bioconjugate chemistry.
- This article is part of the themed collection: Chemical Biology in OBC
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