Glycoconjugated Metallohelices have Improved Nuclear Delivery and Suppress Tumour Growth In Vivo

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F20%3A00533242" target="_blank" >RIV/68081707:_____/20:00533242 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/20:73603647

Výsledek na webu

<a href="https://onlinelibrary.wiley.com/doi/10.1002/anie.202006814" target="_blank" >https://onlinelibrary.wiley.com/doi/10.1002/anie.202006814</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/anie.202006814" target="_blank" >10.1002/anie.202006814</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Glycoconjugated Metallohelices have Improved Nuclear Delivery and Suppress Tumour Growth In Vivo

Popis výsledku v původním jazyce

Monosaccharides are added to the hydrophilic face of a self-assembled asymmetric Fe(II)metallohelix, using CuAAC chemistry. The sixteen resulting architectures are water-stable and optically pure, and exhibit improved antiproliferative selectivity against colon cancer cells (HCT116 p53(+/+)) with respect to the non-cancerous ARPE-19 cell line. While the most selective compound is a glucose-appended enantiomer, its cellular entry is not mainly glucose transporter-mediated. Glucose conjugation nevertheless increases nuclear delivery ca 2.5-fold, and a non-destructive interaction with DNA is indicated. Addition of the glucose units affects the binding orientation of the metallohelix to naked DNA, but does not substantially alter the overall affinity. In a mouse model, the glucose conjugated compound was far better tolerated, and tumour growth delays for the parent compound (2.6 d) were improved to 4.3 d, performance as good as cisplatin but with the advantage of no weight loss in the subjects.

Název v anglickém jazyce

Glycoconjugated Metallohelices have Improved Nuclear Delivery and Suppress Tumour Growth In Vivo

Popis výsledku anglicky

Monosaccharides are added to the hydrophilic face of a self-assembled asymmetric Fe(II)metallohelix, using CuAAC chemistry. The sixteen resulting architectures are water-stable and optically pure, and exhibit improved antiproliferative selectivity against colon cancer cells (HCT116 p53(+/+)) with respect to the non-cancerous ARPE-19 cell line. While the most selective compound is a glucose-appended enantiomer, its cellular entry is not mainly glucose transporter-mediated. Glucose conjugation nevertheless increases nuclear delivery ca 2.5-fold, and a non-destructive interaction with DNA is indicated. Addition of the glucose units affects the binding orientation of the metallohelix to naked DNA, but does not substantially alter the overall affinity. In a mouse model, the glucose conjugated compound was far better tolerated, and tumour growth delays for the parent compound (2.6 d) were improved to 4.3 d, performance as good as cisplatin but with the advantage of no weight loss in the subjects.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

<a href="/cs/project/GA18-09502S" target="_blank" >GA18-09502S: Ovlivnění rezistence nádorových buněk k chemoterapii s cílem obnovit jejich citlivost k novým, existujícím a dosud neúspěšným metalofarmakům</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

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

—

Svazek periodika

59

Číslo periodika v rámci svazku

34

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

9

Strana od-do

14677-14685

Kód UT WoS článku

000545690300001

EID výsledku v databázi Scopus

2-s2.0-85087621111