Transforming Aryl-Tetrazines into Bioorthogonal Scissors for Systematic Cleavage of trans-Cyclooctenes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00601198" target="_blank" >RIV/61388963:_____/25:00601198 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60461373:22330/25:43931851

Výsledek na webu

<a href="https://doi.org/10.1002/anie.202411707" target="_blank" >https://doi.org/10.1002/anie.202411707</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/anie.202411707" target="_blank" >10.1002/anie.202411707</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Transforming Aryl-Tetrazines into Bioorthogonal Scissors for Systematic Cleavage of trans-Cyclooctenes

Popis výsledku v původním jazyce

Bioorthogonal bond-cleavage reactions have emerged as a powerful tool for precise spatiotemporal control of (bio)molecular function in the biological context. Among these chemistries, the tetrazine-triggered elimination of cleavable trans-cyclooctenes (click-to-release) stands out due to high reaction rates, versatility, and selectivity. Despite an increasing understanding of the underlying mechanisms, application of this reaction remains limited by the cumulative performance trade-offs (i.e., click kinetics, release kinetics, release yield) of existing tools. Efficient release has been restricted to tetrazine scaffolds with comparatively low click reactivity, while highly reactive aryl-tetrazines give only minimal release. By introducing hydroxyl groups onto phenyl- and pyridyl-tetrazine scaffolds, we have developed a new class of 'bioorthogonal scissors' with unique chemical performance. We demonstrate that hydroxyaryl-tetrazines achieve near-quantitative release upon accelerated click reaction with cleavable trans-cyclooctenes, as exemplified by click-triggered activation of a caged prodrug, intramitochondrial cleavage of a fluorogenic probe (turn-on) in live cells, and rapid intracellular bioorthogonal disassembly (turn-off) of a ligand-dye conjugate.

Název v anglickém jazyce

Transforming Aryl-Tetrazines into Bioorthogonal Scissors for Systematic Cleavage of trans-Cyclooctenes

Popis výsledku anglicky

Bioorthogonal bond-cleavage reactions have emerged as a powerful tool for precise spatiotemporal control of (bio)molecular function in the biological context. Among these chemistries, the tetrazine-triggered elimination of cleavable trans-cyclooctenes (click-to-release) stands out due to high reaction rates, versatility, and selectivity. Despite an increasing understanding of the underlying mechanisms, application of this reaction remains limited by the cumulative performance trade-offs (i.e., click kinetics, release kinetics, release yield) of existing tools. Efficient release has been restricted to tetrazine scaffolds with comparatively low click reactivity, while highly reactive aryl-tetrazines give only minimal release. By introducing hydroxyl groups onto phenyl- and pyridyl-tetrazine scaffolds, we have developed a new class of 'bioorthogonal scissors' with unique chemical performance. We demonstrate that hydroxyaryl-tetrazines achieve near-quantitative release upon accelerated click reaction with cleavable trans-cyclooctenes, as exemplified by click-triggered activation of a caged prodrug, intramitochondrial cleavage of a fluorogenic probe (turn-on) in live cells, and rapid intracellular bioorthogonal disassembly (turn-off) of a ligand-dye conjugate.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Angewandte Chemie - International Edition

ISSN

1433-7851

e-ISSN

1521-3773

Svazek periodika

64

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

11

Strana od-do

e202411707

Kód UT WoS článku

001354568600001

EID výsledku v databázi Scopus

2-s2.0-85208219434