The Effect of 2′F-RNA on I-Motif Structure and Stability

This article belongs to the Special Issue Chemistry of Nucleic Acids: From Structure to Biological Interactions.

Bibliographic Details
Authors: Ugedo, Cristina, Domínguez, Arnau, Gómez-Pinto, Irene, Eritja, Ramon, González, Carlos, Aviñó, Anna
Format: article
Status:Published version
Publication Date:2025
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/399043
Online Access:http://hdl.handle.net/10261/399043
Access Level:Open access
Keyword:I-motif
NMR
Non-canonical nucleic acids
XNA
Fluorine substitution
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spelling The Effect of 2′F-RNA on I-Motif Structure and StabilityUgedo, CristinaDomínguez, ArnauGómez-Pinto, IreneEritja, RamonGonzález, CarlosAviñó, AnnaI-motifNMRNon-canonical nucleic acidsXNAFluorine substitutionThis article belongs to the Special Issue Chemistry of Nucleic Acids: From Structure to Biological Interactions.[Data Availability Statement] The data underlying this article are available in the Protein Data Bank (PDB) at https://www.rcsb.org/, and can be accessed with IDs 9S6Z and 9S6I for FR1 and FR2, respectively (Extended PDB ID pdb_00009S6Z, BMRB ID 35011 and PDB ID 9S6I, Extended PDB ID pdb_00009S6I, BMRB ID 35010). All other data are available in the article or Supplementary information. Raw data will be shared on request to the corresponding/first authors.I-motifs are non-canonical, cytosine-rich DNA structures stabilized by hemiprotonated C•C+ base pairs, whose formation is highly pH-dependent. While certain chemical modifications can enhance i-motif stability, modifications at the sugar moiety often disrupt essential inter-strand contacts. In this study, we examine the structural and thermodynamic impact of incorporating 2′-fluoro-ribocytidine (2′F-riboC) into i-motif-forming sequences derived from d(TCCCCC). Using a combination of UV, 1H NMR, and 19F NMR spectroscopy, we demonstrate that full substitution with 2′F-riboC strongly destabilizes i-motif, whereas partial substitutions (one or two substitutions per strand) support well-folded structures at acidic pH (pH 5). High-resolution NMR structures reveal well-defined i-motif architectures with conserved C•C+ pairing and characteristic interstrand NOEs. Sugar conformational analysis reveals a predominant North pucker for cytosines, which directs the fluorine substituent toward the minor groove of the i-motif. 19F NMR further confirms slow exchange between folded and unfolded species, enabling the simultaneous detection of both under identical experimental conditions and, consequently, highlighting the utility of fluorine at the 2′ sugar position as a spectroscopic probe. These findings provide insights into fluorine-mediated modulation of i-motif stability and further extend the utility of 19F NMR in nucleic acid research.This research was funded by research grants from the Spanish “Ministerio de Ciencia, Universidades e Innovación” (PID2020-116620GB-I00, PID2023-146366NB-I00, PID2023-148655OB-I00) and CDTI-ISCIII (PMTPA23/00008, XNA-Hub). C.U. is funded by a “Fundación Ramón Areces” fellowship.Peer reviewedMultidisciplinary Digital Publishing InstituteAgencia Estatal de Investigación (España)Ministerio de Ciencia, Innovación y Universidades (España)European CommissionInstituto de Salud Carlos IIIFundación Ramón ArecesUgedo, Cristina [0009-0009-7388-3610]Domínguez, Arnau [0000-0002-4336-9209]González, Carlos [0000-0001-8796-1282]Aviñó, Anna [0000-0003-3047-738X]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2025202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/399043reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-116620GB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2023-146366NB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2023-148655OB-I00The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.3390/molecules30173561https://doi.org/10.3390/molecules30173561Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3990432026-05-22T06:33:51Z
dc.title.none.fl_str_mv The Effect of 2′F-RNA on I-Motif Structure and Stability
title The Effect of 2′F-RNA on I-Motif Structure and Stability
spellingShingle The Effect of 2′F-RNA on I-Motif Structure and Stability
Ugedo, Cristina
I-motif
NMR
Non-canonical nucleic acids
XNA
Fluorine substitution
title_short The Effect of 2′F-RNA on I-Motif Structure and Stability
title_full The Effect of 2′F-RNA on I-Motif Structure and Stability
title_fullStr The Effect of 2′F-RNA on I-Motif Structure and Stability
title_full_unstemmed The Effect of 2′F-RNA on I-Motif Structure and Stability
title_sort The Effect of 2′F-RNA on I-Motif Structure and Stability
dc.creator.none.fl_str_mv Ugedo, Cristina
Domínguez, Arnau
Gómez-Pinto, Irene
Eritja, Ramon
González, Carlos
Aviñó, Anna
author Ugedo, Cristina
author_facet Ugedo, Cristina
Domínguez, Arnau
Gómez-Pinto, Irene
Eritja, Ramon
González, Carlos
Aviñó, Anna
author_role author
author2 Domínguez, Arnau
Gómez-Pinto, Irene
Eritja, Ramon
González, Carlos
Aviñó, Anna
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Agencia Estatal de Investigación (España)
Ministerio de Ciencia, Innovación y Universidades (España)
European Commission
Instituto de Salud Carlos III
Fundación Ramón Areces
Ugedo, Cristina [0009-0009-7388-3610]
Domínguez, Arnau [0000-0002-4336-9209]
González, Carlos [0000-0001-8796-1282]
Aviñó, Anna [0000-0003-3047-738X]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv I-motif
NMR
Non-canonical nucleic acids
XNA
Fluorine substitution
topic I-motif
NMR
Non-canonical nucleic acids
XNA
Fluorine substitution
description This article belongs to the Special Issue Chemistry of Nucleic Acids: From Structure to Biological Interactions.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/399043
url http://hdl.handle.net/10261/399043
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
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#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-116620GB-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2023-146366NB-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2023-148655OB-I00
The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.3390/molecules30173561
https://doi.org/10.3390/molecules30173561
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
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