Optically Pure Metallohelices That Accumulate in Cell Nuclei, Condense/Aggregate DNA, and Inhibit Activities of DNA Processing Enzymes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F20%3A00523950" target="_blank" >RIV/68081707:_____/20:00523950 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/20:73603668

Výsledek na webu

<a href="https://pubs.acs.org/doi/pdf/10.1021/acs.inorgchem.0c00092" target="_blank" >https://pubs.acs.org/doi/pdf/10.1021/acs.inorgchem.0c00092</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.inorgchem.0c00092" target="_blank" >10.1021/acs.inorgchem.0c00092</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Optically Pure Metallohelices That Accumulate in Cell Nuclei, Condense/Aggregate DNA, and Inhibit Activities of DNA Processing Enzymes

Popis výsledku v původním jazyce

The water-compatible optically pure metallohelices made by self-assembly of simple nonpeptidic organic components around Fe(II) ions are now recognized as a distinct subclass of helicates that exhibit similar architecture to some natural cationic antimicrobial peptides. Notably, a new series of metallohelices was recently shown to exhibit biological activity, displaying high, structure-dependent activity against bacteria. It is also important that, thanks to their properties, such metallohelices can exhibit specific interactions with biomacromolecules. Here, following our prior report on the metallohelices that have high, structure-dependent activity against bacteria, we investigated the interactions of the series of iron(II) metallohelices with DNA, which is a potential pharmacological target of this class of coordination compounds. The results obtained with the aid of biophysical and molecular biology methods show that the investigated metallohelices accumulate in eukaryotic cells and that a significant fraction of the metallohelices accumulates in the cell nucleus, allowing them to interact also with nuclear DNA. Additionally, we have demonstrated that some metallohelices have a high affinity to DNA and are able to condense/aggregate DNA molecules more efficiently than conventional DNA-condensing agents, such as polyamines. Moreover, this capability of the metallohelices correlates with their efficiency to inhibit DNA-related enzymatic activities, such as those connected with DNA transcription, catalysis of DNA relaxation by DNA topoisomerase 1, and cleavage by restriction enzymes.

Název v anglickém jazyce

Optically Pure Metallohelices That Accumulate in Cell Nuclei, Condense/Aggregate DNA, and Inhibit Activities of DNA Processing Enzymes

Popis výsledku anglicky

The water-compatible optically pure metallohelices made by self-assembly of simple nonpeptidic organic components around Fe(II) ions are now recognized as a distinct subclass of helicates that exhibit similar architecture to some natural cationic antimicrobial peptides. Notably, a new series of metallohelices was recently shown to exhibit biological activity, displaying high, structure-dependent activity against bacteria. It is also important that, thanks to their properties, such metallohelices can exhibit specific interactions with biomacromolecules. Here, following our prior report on the metallohelices that have high, structure-dependent activity against bacteria, we investigated the interactions of the series of iron(II) metallohelices with DNA, which is a potential pharmacological target of this class of coordination compounds. The results obtained with the aid of biophysical and molecular biology methods show that the investigated metallohelices accumulate in eukaryotic cells and that a significant fraction of the metallohelices accumulates in the cell nucleus, allowing them to interact also with nuclear DNA. Additionally, we have demonstrated that some metallohelices have a high affinity to DNA and are able to condense/aggregate DNA molecules more efficiently than conventional DNA-condensing agents, such as polyamines. Moreover, this capability of the metallohelices correlates with their efficiency to inhibit DNA-related enzymatic activities, such as those connected with DNA transcription, catalysis of DNA relaxation by DNA topoisomerase 1, and cleavage by restriction enzymes.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10402 - Inorganic and nuclear 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

Inorganic Chemistry

ISSN

0020-1669

e-ISSN

—

Svazek periodika

59

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

8

Strana od-do

3304-3311

Kód UT WoS článku

000518088800077

EID výsledku v databázi Scopus

2-s2.0-85080963112