In Vitro Evaluation of Bis-3-Chloropiperidines as RNA Modulators Targeting TAR and TAR-Protein Interaction

After a long limbo, RNA has gained its credibility as a druggable target, fully earning its deserved role in the next generation of pharmaceutical R&D. We have recently probed the trans-activation response (TAR) element, an RNA stem–bulge–loop domain of the HIV-1 genome with bis-3-chloropiperidi...

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Autores principales: Sosic, Alice, Olivato, Giulia, Carraro, Caterina, Göttlich, Richard, Fabris, Dan, Gatto, Barbara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8776071/
https://www.ncbi.nlm.nih.gov/pubmed/35054766
http://dx.doi.org/10.3390/ijms23020582
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author Sosic, Alice
Olivato, Giulia
Carraro, Caterina
Göttlich, Richard
Fabris, Dan
Gatto, Barbara
author_facet Sosic, Alice
Olivato, Giulia
Carraro, Caterina
Göttlich, Richard
Fabris, Dan
Gatto, Barbara
author_sort Sosic, Alice
collection PubMed
description After a long limbo, RNA has gained its credibility as a druggable target, fully earning its deserved role in the next generation of pharmaceutical R&D. We have recently probed the trans-activation response (TAR) element, an RNA stem–bulge–loop domain of the HIV-1 genome with bis-3-chloropiperidines (B-CePs), and revealed the compounds unique behavior in stabilizing TAR structure, thus impairing in vitro the chaperone activity of the HIV-1 nucleocapsid (NC) protein. Seeking to elucidate the determinants of B-CePs inhibition, we have further characterized here their effects on the target TAR and its NC recognition, while developing quantitative analytical approaches for the study of multicomponent RNA-based interactions.
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spelling pubmed-87760712022-01-21 In Vitro Evaluation of Bis-3-Chloropiperidines as RNA Modulators Targeting TAR and TAR-Protein Interaction Sosic, Alice Olivato, Giulia Carraro, Caterina Göttlich, Richard Fabris, Dan Gatto, Barbara Int J Mol Sci Article After a long limbo, RNA has gained its credibility as a druggable target, fully earning its deserved role in the next generation of pharmaceutical R&D. We have recently probed the trans-activation response (TAR) element, an RNA stem–bulge–loop domain of the HIV-1 genome with bis-3-chloropiperidines (B-CePs), and revealed the compounds unique behavior in stabilizing TAR structure, thus impairing in vitro the chaperone activity of the HIV-1 nucleocapsid (NC) protein. Seeking to elucidate the determinants of B-CePs inhibition, we have further characterized here their effects on the target TAR and its NC recognition, while developing quantitative analytical approaches for the study of multicomponent RNA-based interactions. MDPI 2022-01-06 /pmc/articles/PMC8776071/ /pubmed/35054766 http://dx.doi.org/10.3390/ijms23020582 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sosic, Alice
Olivato, Giulia
Carraro, Caterina
Göttlich, Richard
Fabris, Dan
Gatto, Barbara
In Vitro Evaluation of Bis-3-Chloropiperidines as RNA Modulators Targeting TAR and TAR-Protein Interaction
title In Vitro Evaluation of Bis-3-Chloropiperidines as RNA Modulators Targeting TAR and TAR-Protein Interaction
title_full In Vitro Evaluation of Bis-3-Chloropiperidines as RNA Modulators Targeting TAR and TAR-Protein Interaction
title_fullStr In Vitro Evaluation of Bis-3-Chloropiperidines as RNA Modulators Targeting TAR and TAR-Protein Interaction
title_full_unstemmed In Vitro Evaluation of Bis-3-Chloropiperidines as RNA Modulators Targeting TAR and TAR-Protein Interaction
title_short In Vitro Evaluation of Bis-3-Chloropiperidines as RNA Modulators Targeting TAR and TAR-Protein Interaction
title_sort in vitro evaluation of bis-3-chloropiperidines as rna modulators targeting tar and tar-protein interaction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8776071/
https://www.ncbi.nlm.nih.gov/pubmed/35054766
http://dx.doi.org/10.3390/ijms23020582
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