Structural Effects of Incorporation of 2'‐Deoxy‐2'2'‐Difluorodeoxycytidine (Gemcitabine) in A‐ and B‐Form Duplexes

We report the structural effect of 2'‐deoxy‐2',2'‐difluorocytidine (dFdC) insertions in the DNA strand of a DNA : RNA hybrid duplex and in a self‐complementary DNA : DNA duplex. In both cases, the modification slightly destabilizes the duplex and provokes minor local distortions that...

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Detalles Bibliográficos
Autores: Cabrero Fernández, Cristina, Martín‐Pintado, Nerea, Mazzini, Stefania, Gargallo, Raimundo, Eritja Casadellà, Ramón, Aviñó, Anna, González, Carlos
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2021
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/240346
Acceso en línea:http://hdl.handle.net/10261/240346
Access Level:acceso abierto
Palabra clave:DNA
RNA
2'‐Deoxy‐2'2'‐Difluorodeoxycytidine (Gemcitabine)
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spelling Structural Effects of Incorporation of 2'‐Deoxy‐2'2'‐Difluorodeoxycytidine (Gemcitabine) in A‐ and B‐Form DuplexesCabrero Fernández, CristinaMartín‐Pintado, NereaMazzini, StefaniaGargallo, RaimundoEritja Casadellà, RamónAviñó, AnnaGonzález, CarlosDNARNA2'‐Deoxy‐2'2'‐Difluorodeoxycytidine (Gemcitabine)We report the structural effect of 2'‐deoxy‐2',2'‐difluorocytidine (dFdC) insertions in the DNA strand of a DNA : RNA hybrid duplex and in a self‐complementary DNA : DNA duplex. In both cases, the modification slightly destabilizes the duplex and provokes minor local distortions that are more pronounced in the case of the DNA : RNA hybrid. Analysis of the solution structures determined by NMR methods show that dFdC is an adaptable derivative that adopts North type sugar conformation when inserted in pure DNA, or a South sugar conformation in the context of DNA : RNA hybrids. In this latter context, South sugar pucker favors the formation of a 2'F⋅⋅H8 attractive interaction with a neighboring purine, which compensates the destabilizing effect of base pair distortions. These interactions share some features with pseudohydrogen bonds described previously in other nucleic acids structures with fluorine modified sugars.This investigation was supported by research grants from the Ministerio de Ciencia e Innovación (BFU2017‐89707‐P, BFU2017‐84415‐R and PID2019‐107158GB‐I00), Piano de Sostegno alla Ricerca 2020‐Linea2 azione B (Defens), Agència de Gestió d′Ajuts Universitaris i de Recerca (AGAUR) Ref. 2017SGR114. We acknowledge the ICTS NANBIOSIS oligonucleotide synthesis platform (U29) from CIBER‐BBN support, and the “Manuel Rico” NMR laboratory (LMR), a node of the ICTS R‐LRB. C. C. acknowledges the FPI contract.Peer reviewedWiley-BlackwellMinisterio de Ciencia e Innovación (España)Eritja Casadellà, Ramón [0000-0001-5383-9334]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202120212021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/240346reponame: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/BFU2017‐89707‐Pinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/BFU2017‐84415‐Rinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019‐107158GB‐I00https://doi.org/10.1002/chem.202100503Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2403462026-05-22T06:33:51Z
dc.title.none.fl_str_mv Structural Effects of Incorporation of 2'‐Deoxy‐2'2'‐Difluorodeoxycytidine (Gemcitabine) in A‐ and B‐Form Duplexes
title Structural Effects of Incorporation of 2'‐Deoxy‐2'2'‐Difluorodeoxycytidine (Gemcitabine) in A‐ and B‐Form Duplexes
spellingShingle Structural Effects of Incorporation of 2'‐Deoxy‐2'2'‐Difluorodeoxycytidine (Gemcitabine) in A‐ and B‐Form Duplexes
Cabrero Fernández, Cristina
DNA
RNA
2'‐Deoxy‐2'2'‐Difluorodeoxycytidine (Gemcitabine)
title_short Structural Effects of Incorporation of 2'‐Deoxy‐2'2'‐Difluorodeoxycytidine (Gemcitabine) in A‐ and B‐Form Duplexes
title_full Structural Effects of Incorporation of 2'‐Deoxy‐2'2'‐Difluorodeoxycytidine (Gemcitabine) in A‐ and B‐Form Duplexes
title_fullStr Structural Effects of Incorporation of 2'‐Deoxy‐2'2'‐Difluorodeoxycytidine (Gemcitabine) in A‐ and B‐Form Duplexes
title_full_unstemmed Structural Effects of Incorporation of 2'‐Deoxy‐2'2'‐Difluorodeoxycytidine (Gemcitabine) in A‐ and B‐Form Duplexes
title_sort Structural Effects of Incorporation of 2'‐Deoxy‐2'2'‐Difluorodeoxycytidine (Gemcitabine) in A‐ and B‐Form Duplexes
dc.creator.none.fl_str_mv Cabrero Fernández, Cristina
Martín‐Pintado, Nerea
Mazzini, Stefania
Gargallo, Raimundo
Eritja Casadellà, Ramón
Aviñó, Anna
González, Carlos
author Cabrero Fernández, Cristina
author_facet Cabrero Fernández, Cristina
Martín‐Pintado, Nerea
Mazzini, Stefania
Gargallo, Raimundo
Eritja Casadellà, Ramón
Aviñó, Anna
González, Carlos
author_role author
author2 Martín‐Pintado, Nerea
Mazzini, Stefania
Gargallo, Raimundo
Eritja Casadellà, Ramón
Aviñó, Anna
González, Carlos
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Eritja Casadellà, Ramón [0000-0001-5383-9334]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv DNA
RNA
2'‐Deoxy‐2'2'‐Difluorodeoxycytidine (Gemcitabine)
topic DNA
RNA
2'‐Deoxy‐2'2'‐Difluorodeoxycytidine (Gemcitabine)
description We report the structural effect of 2'‐deoxy‐2',2'‐difluorocytidine (dFdC) insertions in the DNA strand of a DNA : RNA hybrid duplex and in a self‐complementary DNA : DNA duplex. In both cases, the modification slightly destabilizes the duplex and provokes minor local distortions that are more pronounced in the case of the DNA : RNA hybrid. Analysis of the solution structures determined by NMR methods show that dFdC is an adaptable derivative that adopts North type sugar conformation when inserted in pure DNA, or a South sugar conformation in the context of DNA : RNA hybrids. In this latter context, South sugar pucker favors the formation of a 2'F⋅⋅H8 attractive interaction with a neighboring purine, which compensates the destabilizing effect of base pair distortions. These interactions share some features with pseudohydrogen bonds described previously in other nucleic acids structures with fluorine modified sugars.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/240346
url http://hdl.handle.net/10261/240346
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #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/BFU2017‐89707‐P
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/BFU2017‐84415‐R
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019‐107158GB‐I00
https://doi.org/10.1002/chem.202100503
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Wiley-Blackwell
publisher.none.fl_str_mv Wiley-Blackwell
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)
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