Control of Tetrazine Bioorthogonal Reactivity by Rotaxanation.

ABSTRACT: Rotaxanation is an efficient method to control the tetrazine-mediated inverse electron demand Diels-Alder (IEDDA) reaction. Tetrazine rotaxanes were synthesized in high yield by crown ether active template applied to the nucleophilic aromatic substitution of tetrazines. Kinetics of the bioorthogonal reaction with tetrazine rotaxanes were much slower than those with the corresponding threads. Interestingly, disassembly of the mechanical bond upon the application of the right stimulus activates IEDDA. Control of IEDDA in live cells was proved by means of a β-galactosidase sensitive tetrazine rotaxane: Enzymatic digestion allowed the Diels-Alder reaction, which resulted in a fluorescent compound.

SUBMITTER: Fumero-Medina C 

PROVIDER: S-EPMC12582004 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature