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Multiple in Vitro Inhibition of HIV‑1 Proteins by 2,6-Dipeptidyl-anthraquinone Conjugates Targeting the PBS RNA
journal contribution
posted on 2020-03-26, 12:08 authored by Elia Gamba, Alice Sosic, Irene Saccone, Elisa Magli, Francesco Frecentese, Barbara GattoWe recently reported
a series of 2,6-dipeptidyl-anthraquinone conjugates
(AQs) as Trans-Activation Response element (TAR) RNA-binding agents
able to inhibit in vitro the HIV-1 nucleocapsid (NC)
protein-mediated processes. Because NC is a highly adaptable nucleic
acid chaperone assisting several crucial steps along reverse transcription,
in this study we investigate the ability of AQs to interact with other
virus-derived nucleic acid structures thus potentially inhibiting
multiple NC functions. Focusing on the HIV-1 Primer Binding Site (PBS)
RNA sequence, we demonstrate that properly substituted dipeptidyl-anthraquinone
conjugates efficiently inhibit the NC-mediated primer annealing in
the low micromolar range. Similarly, we extended the analysis to the
HIV-1 trans-activator of transcription (Tat) peptide, which has been
recently shown to mimic the annealer functions of NC upon interacting
with the same nucleic acid regulatory sequences. Our results highlight
how RNA-targeting agents can act as multimode inhibitors of key viral
proteins affecting their chaperone activity in reverse transcription
processes.
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Trans-Activation Response elementacid structuresRNA-targeting agentsPrimer Binding SiteNC functionsRNA-binding agentsmicromolar rangetranscription processesHIVNC-mediated primer annealingchaperone activityRNA sequenceannealer functionsprotein-mediated processesdipeptidyl-anthraquinone conjugatesAQacid chaperoneVitro InhibitionTARmultimode inhibitorsPBS RNA
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