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• W4313234041 abstract "RNA structure plays an important role in regulating cellular function and there is a significant emerging interest in targeting RNA for drug discovery. Here we report the identification of 4-aminoquinolines as modulators of RNA structure and function. Aminoquinolines have a broad range of pharmacological activities, but their specific mechanism of action is often not fully understood. Using electrophoretic mobility shift assays and enzymatic probing we identified 4-aminoquinolines that bind the stem-loop II motif (s2m) of SARS-CoV-2 RNA site-specifically and induce dimerization. Using fluorescence-based RNA binding and T-box riboswitch functional assays we identified that hydroxychloroquine binds the T-box riboswitch antiterminator RNA element and inhibits riboswitch function. Based on its structure and riboswitch dose-response activity we identified that the antagonist activity of hydroxychloroquine is consistent with it being a conformationally restricted analog of the polyamine spermidine. Given the known role that polyamines play in RNA function, the identification of an RNA binding ligand with the pharmacophore of a conformationally restricted polyamine has significant implications for further elucidation of RNA structure-function relationships and RNA-targeted drug discovery." @default.
• W4313234041 created "2023-01-06" @default.
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• W4313234041 date "2023-02-01" @default.
• W4313234041 modified "2023-10-15" @default.
• W4313234041 title "4-Aminoquinolines modulate RNA structure and function: Pharmacophore implications of a conformationally restricted polyamine" @default.
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• W4313234041 doi "https://doi.org/10.1016/j.bbrc.2022.12.080" @default.
• W4313234041 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36630735" @default.
• W4313234041 hasPublicationYear "2023" @default.
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