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5′-Phosphonate modified oligoadenylates as potent activators of human RNase L
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SYSNO ASEP 0552686 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title 5′-Phosphonate modified oligoadenylates as potent activators of human RNase L Author(s) Lášek, Tomáš (UOCHB-X) ORCID
Petrová, Magdalena (UOCHB-X) RID
Markusová Kóšiová, Ivana (UOCHB-X) RID, ORCID
Šimák, Ondřej (UOCHB-X) RID
Buděšínský, Miloš (UOCHB-X) RID, ORCID
Kozák, Jaroslav (UOCHB-X) RID, ORCID
Snášel, Jan (UOCHB-X) RID
Vavřina, Zdeněk (UOCHB-X) ORCID
Birkuš, Gabriel (UOCHB-X) ORCID
Rosenberg, Ivan (UOCHB-X) RID, ORCID
Páv, Ondřej (UOCHB-X) RID, ORCIDArticle number 116632 Source Title Bioorganic & Medicinal Chemistry. - : Elsevier - ISSN 0968-0896
Roč. 56, Feb 15 (2022)Number of pages 9 s. Language eng - English Country GB - United Kingdom Keywords RNase L ; Oligoadenylate ; Phosphonate oligonucleotide ; OAS-RNase L pathway ; 2-5A OECD category Biochemistry and molecular biology R&D Projects EF16_019/0000729 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Limited access Institutional support UOCHB-X - RVO:61388963 UT WOS 000968229100006 EID SCOPUS 85123194690 DOI 10.1016/j.bmc.2022.116632 Annotation 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. Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Year of Publishing 2023 Electronic address https://doi.org/10.1016/j.bmc.2022.116632
Number of the records: 1