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Repurpsing Antiviral Drugs for Orthogonal RNA-Catalyzed Labeling

Please always quote using this URN: urn:nbn:de:bvb:20-opus-205552
  • In vitro selected ribozymes are promising tools for site-specific labeling of RNA. Previously known nucleic acid catalysts attached fluorescently labeled adenosine or guanosine derivatives through 2’,5’-branched phosphodiester bonds to the RNA of interest. Herein, we report new ribozymes that use orthogonal substrates, derived from the antiviral drug tenofovir, and attach bioorthogonal functional groups, as well as affinity handles and fluorescent reporter units through a hydrolytically more stable phosphonate ester linkage. The tenofovirIn vitro selected ribozymes are promising tools for site-specific labeling of RNA. Previously known nucleic acid catalysts attached fluorescently labeled adenosine or guanosine derivatives through 2’,5’-branched phosphodiester bonds to the RNA of interest. Herein, we report new ribozymes that use orthogonal substrates, derived from the antiviral drug tenofovir, and attach bioorthogonal functional groups, as well as affinity handles and fluorescent reporter units through a hydrolytically more stable phosphonate ester linkage. The tenofovir transferase ribozymes were identified by in vitro selection and are orthogonal to nucleotide transferase ribozymes. As genetically encodable functional RNAs, these ribozymes may be developed for potential cellular applications. The orthogonal ribozymes addressed desired target sites in large RNAs in vitro, as shown by fluorescent labeling of E. coli 16S and 23S RNAs in total cellular RNA.show moreshow less

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Author: Mohammad Ghaem Maghami, Surjendu Dey, Ann-Kathrin Lenz, Claudia HöbartnerORCiD
URN:urn:nbn:de:bvb:20-opus-205552
Document Type:Journal article
Faculties:Fakultät für Chemie und Pharmazie / Institut für Organische Chemie
Language:English
Parent Title (English):Angewandte Chemie, International Edition
Year of Completion:2020
Volume:59
Pagenumber:9335–9339
Source:Angewandte Chemie, International Edition 2020, 59 , 9335-9339. https://doi.org/10.1002/anie.202001300
DOI:https://doi.org/https://doi.org/10.1002/ange.202001300
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 54 Chemie / 547 Organische Chemie
Tag:Antiviral nucleoside analogues; in vitro selection; ribozymes; site-specific RNA labeling; tenofovir
Release Date:2020/06/09
EU-Project number / Contract (GA) number:682586
OpenAIRE:OpenAIRE
Licence (German):License LogoCC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitungen 4.0 International