Development of linear β-turn inducers containing peptides as arc mimetics with DNA topological and sequence selectivity

In general, biological macromolecules such as proteins interact with the major groove of the ds-DNA via hydrogen bonds formation, thus blocking the site access of TFs to specific DNA sequences. Considering that the primary sequence of arc repressor responsible for DNA binding is well-characterized a...

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Autores: Stefanucci, Azzurra, Santoro, Federica, D’Ingiullo, Sara, Marinaccio, Lorenza, Procino, Eleonora, Learte Aymamí, Soraya, Rodríguez Villar, Jéssica, Mascareñas Cid, José Luis, Amato, Jussara, Arciuolo, Valentina, Randazzo, Antonio, De Rosa, Martina, Brancaccio, Diego, Mollica, Adriano, Carotenuto, Alfonso
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universidad de Santiago de Compostela (USC)
Repositorio:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
Idioma:inglés
OAI Identifier:oai:minerva.usc.gal:10347/41167
Acceso en línea:https://hdl.handle.net/10347/41167
Access Level:acceso abierto
Palabra clave:Arc mimetic
Peptides
DNA major groove
β-hairpin
2306 Química orgánica
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spelling Development of linear β-turn inducers containing peptides as arc mimetics with DNA topological and sequence selectivityStefanucci, AzzurraSantoro, FedericaD’Ingiullo, SaraMarinaccio, LorenzaProcino, EleonoraLearte Aymamí, SorayaRodríguez Villar, JéssicaMascareñas Cid, José LuisAmato, JussaraArciuolo, ValentinaRandazzo, AntonioDe Rosa, MartinaBrancaccio, DiegoMollica, AdrianoCarotenuto, AlfonsoArc mimeticPeptidesDNA major grooveβ-hairpin2306 Química orgánicaIn general, biological macromolecules such as proteins interact with the major groove of the ds-DNA via hydrogen bonds formation, thus blocking the site access of TFs to specific DNA sequences. Considering that the primary sequence of arc repressor responsible for DNA binding is well-characterized as well as the 3D-conformational requisites for its optimal interactions with the specific DNA base-pairs, a series of well-tailored arc analogues could be designed using computational molecular tools and available structural data. These novel molecular entities have been synthesized following ultrasound assisted-solid phase peptide synthesis (US-SPPS), characterized by NMR experiments and screened for TAGA box selectivity on DNA oligomers using a battery of DNA displacement assays. Data obtained show a clear tendency of peptide ACAS_4 to assume a 3-D β-sheet like structure responsible of the interaction with DNA major groove and to bind selectively to the consensus sequence of DNA. For the best of our knowledge this is the first report on a β-sheet arc mimetic endowed with topological and sequence selectivity for the TAGA box of DNA.ElsevierUniversidade de Santiago de Compostela. Departamento de Química OrgánicaUniversidade de Santiago de Compostela. Centro de Investigación en Química Biolóxica e Materiais Moleculares (CiQUS)20252025-05-0120252025-05-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10347/41167reponame:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostelainstname:Universidad de Santiago de Compostela (USC)InglésengAgencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023 PID2023-146174NA-I00 FUNCIONALIZACION QUIMIOSELECTIVA DE BIOMOLECULAS MEDIADA POR METALESopen accesshttp://purl.org/coar/access_right/c_abf2© 2025 The Authors. Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ).http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:minerva.usc.gal:10347/411672026-06-15T12:47:27Z
dc.title.none.fl_str_mv Development of linear β-turn inducers containing peptides as arc mimetics with DNA topological and sequence selectivity
title Development of linear β-turn inducers containing peptides as arc mimetics with DNA topological and sequence selectivity
spellingShingle Development of linear β-turn inducers containing peptides as arc mimetics with DNA topological and sequence selectivity
Stefanucci, Azzurra
Arc mimetic
Peptides
DNA major groove
β-hairpin
2306 Química orgánica
title_short Development of linear β-turn inducers containing peptides as arc mimetics with DNA topological and sequence selectivity
title_full Development of linear β-turn inducers containing peptides as arc mimetics with DNA topological and sequence selectivity
title_fullStr Development of linear β-turn inducers containing peptides as arc mimetics with DNA topological and sequence selectivity
title_full_unstemmed Development of linear β-turn inducers containing peptides as arc mimetics with DNA topological and sequence selectivity
title_sort Development of linear β-turn inducers containing peptides as arc mimetics with DNA topological and sequence selectivity
dc.creator.none.fl_str_mv Stefanucci, Azzurra
Santoro, Federica
D’Ingiullo, Sara
Marinaccio, Lorenza
Procino, Eleonora
Learte Aymamí, Soraya
Rodríguez Villar, Jéssica
Mascareñas Cid, José Luis
Amato, Jussara
Arciuolo, Valentina
Randazzo, Antonio
De Rosa, Martina
Brancaccio, Diego
Mollica, Adriano
Carotenuto, Alfonso
author Stefanucci, Azzurra
author_facet Stefanucci, Azzurra
Santoro, Federica
D’Ingiullo, Sara
Marinaccio, Lorenza
Procino, Eleonora
Learte Aymamí, Soraya
Rodríguez Villar, Jéssica
Mascareñas Cid, José Luis
Amato, Jussara
Arciuolo, Valentina
Randazzo, Antonio
De Rosa, Martina
Brancaccio, Diego
Mollica, Adriano
Carotenuto, Alfonso
author_role author
author2 Santoro, Federica
D’Ingiullo, Sara
Marinaccio, Lorenza
Procino, Eleonora
Learte Aymamí, Soraya
Rodríguez Villar, Jéssica
Mascareñas Cid, José Luis
Amato, Jussara
Arciuolo, Valentina
Randazzo, Antonio
De Rosa, Martina
Brancaccio, Diego
Mollica, Adriano
Carotenuto, Alfonso
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade de Santiago de Compostela. Departamento de Química Orgánica
Universidade de Santiago de Compostela. Centro de Investigación en Química Biolóxica e Materiais Moleculares (CiQUS)
dc.subject.none.fl_str_mv Arc mimetic
Peptides
DNA major groove
β-hairpin
2306 Química orgánica
topic Arc mimetic
Peptides
DNA major groove
β-hairpin
2306 Química orgánica
description In general, biological macromolecules such as proteins interact with the major groove of the ds-DNA via hydrogen bonds formation, thus blocking the site access of TFs to specific DNA sequences. Considering that the primary sequence of arc repressor responsible for DNA binding is well-characterized as well as the 3D-conformational requisites for its optimal interactions with the specific DNA base-pairs, a series of well-tailored arc analogues could be designed using computational molecular tools and available structural data. These novel molecular entities have been synthesized following ultrasound assisted-solid phase peptide synthesis (US-SPPS), characterized by NMR experiments and screened for TAGA box selectivity on DNA oligomers using a battery of DNA displacement assays. Data obtained show a clear tendency of peptide ACAS_4 to assume a 3-D β-sheet like structure responsible of the interaction with DNA major groove and to bind selectively to the consensus sequence of DNA. For the best of our knowledge this is the first report on a β-sheet arc mimetic endowed with topological and sequence selectivity for the TAGA box of DNA.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025-05-01
2025
2025-05-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10347/41167
url https://hdl.handle.net/10347/41167
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023 PID2023-146174NA-I00 FUNCIONALIZACION QUIMIOSELECTIVA DE BIOMOLECULAS MEDIADA POR METALES
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
instname:Universidad de Santiago de Compostela (USC)
instname_str Universidad de Santiago de Compostela (USC)
reponame_str Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
collection Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812455

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