Structurally Redesigned Bioorthogonal Reagents for Mitochondria-Specific Prodrug Activation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F21%3A00538814" target="_blank" >RIV/61388963:_____/21:00538814 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68378041:_____/21:00538814

Výsledek na webu

<a href="https://doi.org/10.1021/jacsau.0c00053" target="_blank" >https://doi.org/10.1021/jacsau.0c00053</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/jacsau.0c00053" target="_blank" >10.1021/jacsau.0c00053</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Structurally Redesigned Bioorthogonal Reagents for Mitochondria-Specific Prodrug Activation

Popis výsledku v původním jazyce

The development of abiotic chemical reactions that can be performed in anorganelle-specific manner can provide new opportunities in drug delivery and cell and chemicalbiology. However, due to the complexity of the cellular environment, this remains a significantchallenge. Here, we introduce structurally redesigned bioorthogonal tetrazine reagents thatspontaneously accumulate in mitochondria of live mammalian cells. The attributes leading totheir efficient accumulation in the organelle were optimized to include the right combinationof lipophilicity and positive delocalized charge. The best performing mitochondriotropictetrazines enable subcellular chemical release of TCO-caged compounds as we show usingfluorogenic substrates and mitochondrial uncoupler niclosamide. Our work demonstrates thata shrewd redesign of common bioorthogonal reagents can lead to their transformation intoorganelle-specific probes, opening the possibility to activate prodrugs and m anipulatebiological processes at the subcellular level by using purely chemical tools.

Název v anglickém jazyce

Structurally Redesigned Bioorthogonal Reagents for Mitochondria-Specific Prodrug Activation

Popis výsledku anglicky

The development of abiotic chemical reactions that can be performed in anorganelle-specific manner can provide new opportunities in drug delivery and cell and chemicalbiology. However, due to the complexity of the cellular environment, this remains a significantchallenge. Here, we introduce structurally redesigned bioorthogonal tetrazine reagents thatspontaneously accumulate in mitochondria of live mammalian cells. The attributes leading totheir efficient accumulation in the organelle were optimized to include the right combinationof lipophilicity and positive delocalized charge. The best performing mitochondriotropictetrazines enable subcellular chemical release of TCO-caged compounds as we show usingfluorogenic substrates and mitochondrial uncoupler niclosamide. Our work demonstrates thata shrewd redesign of common bioorthogonal reagents can lead to their transformation intoorganelle-specific probes, opening the possibility to activate prodrugs and m anipulatebiological processes at the subcellular level by using purely chemical tools.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

10401 - Organic chemistry

Projekt

<a href="/cs/project/GA19-13811S" target="_blank" >GA19-13811S: Konstrukce syntetických látek umožňujících uvolňování malých molekul v specifických buněčných organelách</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

JACS Au

ISSN

2691-3704

e-ISSN

2691-3704

Svazek periodika

1

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

8

Strana od-do

23-30

Kód UT WoS článku

000651111900005

EID výsledku v databázi Scopus

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