Sulfonated Hydroxyaryl-Tetrazines with Increased pKa for Accelerated Bioorthogonal Click-to-Release Reactions in Cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00599804" target="_blank" >RIV/61388963:_____/25:00599804 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60461373:22330/25:43931852

Výsledek na webu

<a href="https://doi.org/10.1002/anie.202411713" target="_blank" >https://doi.org/10.1002/anie.202411713</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/anie.202411713" target="_blank" >10.1002/anie.202411713</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Sulfonated Hydroxyaryl-Tetrazines with Increased pKa for Accelerated Bioorthogonal Click-to-Release Reactions in Cells

Popis výsledku v původním jazyce

Bioorthogonal reactions that enable switching molecular functions by breaking chemical bonds have gained prominence, with the tetrazine-mediated cleavage of trans-cyclooctene caged compounds (click-to-release) being particularly noteworthy for its high versatility, biocompatibility, and fast reaction rates. Despite several recent advances, the development of highly reactive tetrazines enabling quantitative elimination from trans-cyclooctene linkers remains challenging. In this study, we present the synthesis and application of sulfo-tetrazines, a class of derivatives featuring phenolic hydroxyl groups with increased acidity constants (pKa). This unique property leads to accelerated elimination and complete release of the caged molecules within minutes. Moreover, the inclusion of sulfonate groups provides a valuable synthetic handle, enabling further derivatization into sulfonamides, modified with diverse substituents. Significantly, we demonstrate the utility of sulfo-tetrazines in efficiently activating fluorogenic compounds and prodrugs in living cells, offering exciting prospects for their application in bioorthogonal chemistry.

Název v anglickém jazyce

Sulfonated Hydroxyaryl-Tetrazines with Increased pKa for Accelerated Bioorthogonal Click-to-Release Reactions in Cells

Popis výsledku anglicky

Bioorthogonal reactions that enable switching molecular functions by breaking chemical bonds have gained prominence, with the tetrazine-mediated cleavage of trans-cyclooctene caged compounds (click-to-release) being particularly noteworthy for its high versatility, biocompatibility, and fast reaction rates. Despite several recent advances, the development of highly reactive tetrazines enabling quantitative elimination from trans-cyclooctene linkers remains challenging. In this study, we present the synthesis and application of sulfo-tetrazines, a class of derivatives featuring phenolic hydroxyl groups with increased acidity constants (pKa). This unique property leads to accelerated elimination and complete release of the caged molecules within minutes. Moreover, the inclusion of sulfonate groups provides a valuable synthetic handle, enabling further derivatization into sulfonamides, modified with diverse substituents. Significantly, we demonstrate the utility of sulfo-tetrazines in efficiently activating fluorogenic compounds and prodrugs in living cells, offering exciting prospects for their application in bioorthogonal chemistry.

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

e202411713

Kód UT WoS článku

001345152800001

EID výsledku v databázi Scopus

2-s2.0-85207773252