Homologues of epigenetic pyrimidines: 5-alkyl-, 5-hydroxyalkyl and 5-acyluracil andcytosine nucleotides: synthesis, enzymatic incorporation into DNA and effect on transcription with bacterial RNA polymerase

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F22%3A00559506" target="_blank" >RIV/61388963:_____/22:00559506 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61388971:_____/22:00559506 RIV/00216208:11310/22:10454619

Výsledek na webu

<a href="https://doi.org/10.1039/D2CB00133K" target="_blank" >https://doi.org/10.1039/D2CB00133K</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/d2cb00133k" target="_blank" >10.1039/d2cb00133k</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Homologues of epigenetic pyrimidines: 5-alkyl-, 5-hydroxyalkyl and 5-acyluracil andcytosine nucleotides: synthesis, enzymatic incorporation into DNA and effect on transcription with bacterial RNA polymerase

Popis výsledku v původním jazyce

Homologues of natural epigenetic pyrimidine nucleosides and nucleotides were designed and synthesized. They included 5-ethyl-, 5-propyl-, 5-(1-hydroxyethyl)-, 5-(1-hydroxypropyl)- and 5-acetyl- and 5-propionyl-cytosine anduracil 2'-deoxyribonucleosides and their corresponding 5'-O-triphosphates (dN(x)TPs). The epimers of 5-(1-hydroxyethyl)- and 5-(1-hydroxypropyl)pyrimidine nucleosides were separated and their absolute configuration was determined by a combination of X-ray and NMR analysis. The modified dN(x)TPs were used as substrates for PCR synthesis of modified DNA templates used for the study of transcription with bacterial RNA polymerase. Fundamental differences in transcription efficiency were observed, depending on the various modifications. The most notable effects included pronounced stimulation of transcription from 5-ethyluracil-bearing templates (200% transcription yield compared to natural thymine) and an enhancing effect of 5-acetylcytosine versus inhibiting effect of 5-acetyluracil. In summary, these results reveal that RNA polymerase copes with dramatically altered DNA structure and suggest that these nucleobases could potentially play roles as artificial epigenetic DNA nucleobases.

Název v anglickém jazyce

Homologues of epigenetic pyrimidines: 5-alkyl-, 5-hydroxyalkyl and 5-acyluracil andcytosine nucleotides: synthesis, enzymatic incorporation into DNA and effect on transcription with bacterial RNA polymerase

Popis výsledku anglicky

Homologues of natural epigenetic pyrimidine nucleosides and nucleotides were designed and synthesized. They included 5-ethyl-, 5-propyl-, 5-(1-hydroxyethyl)-, 5-(1-hydroxypropyl)- and 5-acetyl- and 5-propionyl-cytosine anduracil 2'-deoxyribonucleosides and their corresponding 5'-O-triphosphates (dN(x)TPs). The epimers of 5-(1-hydroxyethyl)- and 5-(1-hydroxypropyl)pyrimidine nucleosides were separated and their absolute configuration was determined by a combination of X-ray and NMR analysis. The modified dN(x)TPs were used as substrates for PCR synthesis of modified DNA templates used for the study of transcription with bacterial RNA polymerase. Fundamental differences in transcription efficiency were observed, depending on the various modifications. The most notable effects included pronounced stimulation of transcription from 5-ethyluracil-bearing templates (200% transcription yield compared to natural thymine) and an enhancing effect of 5-acetylcytosine versus inhibiting effect of 5-acetyluracil. In summary, these results reveal that RNA polymerase copes with dramatically altered DNA structure and suggest that these nucleobases could potentially play roles as artificial epigenetic DNA nucleobases.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

RSC Chemical Biology

ISSN

2633-0679

e-ISSN

2633-0679

Svazek periodika

3

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

7

Strana od-do

1069-1075

Kód UT WoS článku

000825796800001

EID výsledku v databázi Scopus

2-s2.0-85134389118