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B-CePs as cross-linking probes for the investigation of RNA higher-order structure.

Authors
  • Sosic, Alice1
  • Göttlich, Richard2
  • Fabris, Dan3
  • Gatto, Barbara1
  • 1 Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy. , (Italy)
  • 2 Institute of Organic Chemistry, Justus Liebig University Giessen, 35392 Giessen, Germany. , (Germany)
  • 3 Departments of Chemistry and Biological Sciences, University at Albany-SUNY, Albany, NY, 12222, USA.
Type
Published Article
Journal
Nucleic Acids Research
Publisher
Oxford University Press
Publication Date
Jun 14, 2021
Identifiers
DOI: 10.1093/nar/gkab468
PMID: 34125908
Source
Medline
Language
English
License
Unknown

Abstract

Elucidating the structure of RNA and RNA ensembles is essential to understand biological functions. In this work, we explored the previously uncharted reactivity of bis-chloropiperidines (B-CePs) towards RNA. We characterized at the molecular level the different adducts induced by the fast reacting compound B-CeP 1 with RNA. Following an approach based on solution thermal melting coupled with ESI mass spectrometry (STHEM-ESI), we proved the ability of B-CePs to induce inter-molecular cross-links between guanines in double stranded RNA. These results open the possibility of using B-CePs as structural probes for investigating higher-order structures, such as the kissing loop complex established by the dimerization initiation site (DIS) of the HIV-1 genome. We confirmed the potential of B-CePs to reveal the identity of RNA structures involved in long-range interactions, expecting to benefit the characterization of samples that are not readily amenable to traditional high-resolution techniques, and thus promoting the elucidation of pertinent RNA systems associated with old and new diseases. © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.

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