Substitution-Inert Polynuclear Platinum Complexes That Inhibit the Activity of DNA Polymerase in Triplex-Forming Templates

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F18%3A00502432" target="_blank" >RIV/68081707:_____/18:00502432 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1002/anie.201803448" target="_blank" >http://dx.doi.org/10.1002/anie.201803448</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/anie.201803448" target="_blank" >10.1002/anie.201803448</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Substitution-Inert Polynuclear Platinum Complexes That Inhibit the Activity of DNA Polymerase in Triplex-Forming Templates

Popis výsledku v původním jazyce

The formation of triple-helical DNA is implicated in the regulation of gene expression. The triplexes are, however, unstable under physiological conditions so that effective stabilizers for the triplex formation are needed. Herein, we describe a new strategy for the stabilization of such triplexes that is based on antitumor substitution-inert polynuclear platinum complexes (SI-PPCs). These compounds were previously shown to bind to DNA through the phosphate clampa discrete mode of DNA-ligand recognition distinct from the canonical intercalation and minor-groove binding. We have found that SI-PPCs efficiently inhibit DNA synthesis by DNA polymerase in sequences prone to the formation of pyrimidine- and purine-motif triplex DNAs. Moreover, the results suggest that SI-PPCs are able to induce the formation of triple-helical DNA between duplexes and strands that are not completely complementary to each other. Collectively, these data provide evidence that SI-PPCs are very efficient stabilizers of triple-stranded DNA that might exert their action by stabilizing higher-order structures such as triple-helical DNA.

Název v anglickém jazyce

Substitution-Inert Polynuclear Platinum Complexes That Inhibit the Activity of DNA Polymerase in Triplex-Forming Templates

Popis výsledku anglicky

The formation of triple-helical DNA is implicated in the regulation of gene expression. The triplexes are, however, unstable under physiological conditions so that effective stabilizers for the triplex formation are needed. Herein, we describe a new strategy for the stabilization of such triplexes that is based on antitumor substitution-inert polynuclear platinum complexes (SI-PPCs). These compounds were previously shown to bind to DNA through the phosphate clampa discrete mode of DNA-ligand recognition distinct from the canonical intercalation and minor-groove binding. We have found that SI-PPCs efficiently inhibit DNA synthesis by DNA polymerase in sequences prone to the formation of pyrimidine- and purine-motif triplex DNAs. Moreover, the results suggest that SI-PPCs are able to induce the formation of triple-helical DNA between duplexes and strands that are not completely complementary to each other. Collectively, these data provide evidence that SI-PPCs are very efficient stabilizers of triple-stranded DNA that might exert their action by stabilizing higher-order structures such as triple-helical DNA.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

<a href="/cs/project/GA16-03517S" target="_blank" >GA16-03517S: Termodynamická analýza sekundárních struktur RNA a jejich interakcí s ligandy</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

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

57

Číslo periodika v rámci svazku

28

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

5

Strana od-do

8535-8539

Kód UT WoS článku

000437668700029

EID výsledku v databázi Scopus

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