Discovery of new tetrazines for bioorthogonal reactions with strained alkenes via computational chemistry.

ABSTRACT: Tetrazines are widely employed reagents in bioorthogonal chemistry, as they react readily with strained alkenes in inverse electron demand Diels-Alder reactions, allowing for selective labeling of biomacromolecules. For optimal performance, tetrazine reagents have to react readily with strained alkenes, while remaining inert against nucleophiles like thiols. Balancing these conditions is a challenge, as reactivity towards strained alkenes and nucleophiles is governed by the same factor - the energy of unoccupied orbitals of tetrazine. Herein, we utilize computational chemistry to screen a set of tetrazine derivatives, aiming to identify structural elements responsible for a better ratio of reactivity with strained alkenes vs. stability against nucleophiles. This advantageous trait i

SUBMITTER: Majek M 

PROVIDER: S-EPMC10828936 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature