Journal article

Publication year: 2021

Pages: 1874-

Journal: Molecules

Volume number: 26

Issue number: 7

Open access status: Gold

DOI Link: https://doi.org/10.3390/molecules26071874

Publisher: MDPI

Abstract: 
Specific RNA sequences regulate functions essential to life. The Trans-Activation Response element (TAR) is an RNA stem-bulge-loop structure involved in several steps of HIV-1 replication. In this work, we show how RNA targeting can inhibit HIV-1 nucleocapsid (NC), a highly conserved protein known to catalyze nucleic acid melting and strand transfers during reverse transcription. Our RNA targeting strategy consists of the employment of bis-3-chloropiperidines (B-CePs) to impair RNA melting through bifunctional alkylation. Specific interactions between B-CePs and TAR RNA were analytically investigated by gel electrophoresis and mass spectrometry, allowing the elucidation of B-CePs' recognition of TAR, and highlighting an RNA-directed mechanism of protein inhibition. We propose that B-CePs can freeze TAR tridimensional conformation, impairing NC-induced dynamics and finally inhibiting its functions in vitro.

Harvard Citation style: Sosic, A., Olivato, G., Carraro, C., Göttlich, R., Fabris, D. and Gatto, B. (2021) Bis-3-Chloropiperidines Targeting TAR RNA as A Novel Strategy to Impair the HIV-1 Nucleocapsid Protein, Molecules, 26(7), p. 1874. https://doi.org/10.3390/molecules26071874

APA Citation style: Sosic, A., Olivato, G., Carraro, C., Göttlich, R., Fabris, D., & Gatto, B. (2021). Bis-3-Chloropiperidines Targeting TAR RNA as A Novel Strategy to Impair the HIV-1 Nucleocapsid Protein. Molecules. 26(7), 1874. https://doi.org/10.3390/molecules26071874