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Multiple in Vitro Inhibition of HIV-1 Proteins by 2,6-Dipeptidyl-anthraquinone Conjugates Targeting the PBS RNA.

Abstract：

:We 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.

journal_name

ACS Med Chem Lett

journal_title

ACS medicinal chemistry letters

authors

Gamba E,Sosic A,Saccone I,Magli E,Frecentese F,Gatto B

doi

10.1021/acsmedchemlett.9b00682

subject

Has Abstract

pub_date

2020-03-23 00:00:00

pages

949-955

issue

5

issn

1948-5875

journal_volume

11

pub_type

杂志文章

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