Repurposing Antiviral Drugs for Orthogonal RNA‐Catalyzed Labeling of RNA. (1st April 2020)

• Record Type: Journal Article
• Authors: Ghaem Maghami, Mohammad; Dey, Surjendu; Lenz, Ann‐Kathrin; Höbartner, Claudia
• Is Part Of: Angewandte Chemie. Volume 132:Number 24(2020)
• Page Start: 9421
• Page End: 9425
• Publication Date: 2020-04-01
• Subjects: antiviral nucleoside analogues -- in vitro selection -- ribozymes -- site-specific RNA labeling -- tenofovir; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202001300
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: 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 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 rRNAs in total cellular RNA. Abstract : A strategy for illuminating RNA with fluorescent derivatives of the antiviral acyclic nucleoside phosphonate Tenofovir is presented. Tenofovir transferase ribozymes were identified by in vitro selection and are shown to be orthogonal to nucleotidyl transferase ribozymes, thus enabling site‐specific dual labeling of RNA.