5′-Phosphonate modified oligoadenylates as potent activators of human RNase L

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F22%3A00552686" target="_blank" >RIV/61388963:_____/22:00552686 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/22:10441482

Výsledek na webu

<a href="https://doi.org/10.1016/j.bmc.2022.116632" target="_blank" >https://doi.org/10.1016/j.bmc.2022.116632</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bmc.2022.116632" target="_blank" >10.1016/j.bmc.2022.116632</a>

Jazyk výsledku

angličtina

Název v původním jazyce

5′-Phosphonate modified oligoadenylates as potent activators of human RNase L

Popis výsledku v původním jazyce

The oligoadenylate synthetase-ribonuclease L pathway is a major player in the interferon-induced antiviral defense mechanism of cells. Upon sensing viral dsRNA, 5'-phosphorylated 2',5'-oligoadenylates are synthesized, and subsequently activate latent RNase L. To determine the influence of 5'-phosphate end on the activation of human RNase L, four sets of 5'-phosphonate modified oligoadenylates were prepared on solid-phase. The ability of these 5'-modified oligoadenylates bearing shortened, isosteric and prolonged phosphonate linkages to activate RNase L was explored. We found that isosteric linkages and linkages prolonged by one atom were in general well tolerated by the enzyme with the EC50 values comparable to that of the natural activator. In contrast, linkages shortened by one atom or prolonged by two atoms exhibited decrease in the activity.

Název v anglickém jazyce

5′-Phosphonate modified oligoadenylates as potent activators of human RNase L

Popis výsledku anglicky

The oligoadenylate synthetase-ribonuclease L pathway is a major player in the interferon-induced antiviral defense mechanism of cells. Upon sensing viral dsRNA, 5'-phosphorylated 2',5'-oligoadenylates are synthesized, and subsequently activate latent RNase L. To determine the influence of 5'-phosphate end on the activation of human RNase L, four sets of 5'-phosphonate modified oligoadenylates were prepared on solid-phase. The ability of these 5'-modified oligoadenylates bearing shortened, isosteric and prolonged phosphonate linkages to activate RNase L was explored. We found that isosteric linkages and linkages prolonged by one atom were in general well tolerated by the enzyme with the EC50 values comparable to that of the natural activator. In contrast, linkages shortened by one atom or prolonged by two atoms exhibited decrease in the activity.

Druh

J_SC - Článek v periodiku v databázi SCOPUS

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/EF16_019%2F0000729" target="_blank" >EF16_019/0000729: Chemická biologie pro vývoj nových terapií</a><br>

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

Bioorganic & Medicinal Chemistry

ISSN

0968-0896

e-ISSN

1464-3391

Svazek periodika

56

Číslo periodika v rámci svazku

Feb 15

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

9

Strana od-do

116632

Kód UT WoS článku

000968229100006

EID výsledku v databázi Scopus

2-s2.0-85123194690