Modified Bis-pyrimidine Clamps for Triplex Formation and Their Usein SARS-CoV‑2 Detection
The formation of nucleic acid triple helices (“triplexes”) is an area of great interest due to their potential role in thenatural and artificial regulation of gene expression or for use in analytical, diagnostic, or synthetic methods. During the coronaviruspandemic, a large search for novel methods...
| Autores: | , , , , , , , , , |
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| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Recursos: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/227188 |
| Acesso em linha: | https://hdl.handle.net/2445/227188 |
| Access Level: | acceso abierto |
| Palavra-chave: | Estructura química Genètica SARS-CoV-2 Chemical structure Genetics |
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Modified Bis-pyrimidine Clamps for Triplex Formation and Their Usein SARS-CoV‑2 DetectionDomínguez, ArnauGargallo Gómez, RaimundoCuestas-Ayllón, CarlosGómez-Pinto, IreneFàbrega, Carmen Martínez de la Fuente, JesúsDamha, M. J.González, CarlosEritja i Casadellà, RamonAviñó Andrés, AnnaEstructura químicaGenèticaSARS-CoV-2Chemical structureGeneticsSARS-CoV-2The formation of nucleic acid triple helices (“triplexes”) is an area of great interest due to their potential role in thenatural and artificial regulation of gene expression or for use in analytical, diagnostic, or synthetic methods. During the coronaviruspandemic, a large search for novel methods for the detection of SARS-CoV-2 was undertaken. Based on triplex affinity capture andusing polypurine reverse-Hoogsteen hairpins, a method known as Triplex Enhanced Nucleic Acid Detection Assay (TENADA) wasdeveloped for the rapid detection of SARS-CoV-2 without the need for polymerase chain reaction (PCR) amplification. In this work,to expand the targeting scope of this method, we explored triplex-forming bis-pyrimidine clamps targeting a polypurine sequence inthe ORF1a region of SARS-CoV-2. To enhance parallel triplex stability, 2′-sugar and 5-methylpyrimidine modifications wereincorporated into both strands of the clamps, and their effect on the triplexes formed was assessed via NMR and other biophysicalmethods. The results revealed distinct stabilizing effects of the modifications, influenced by their size, sugar puckering, and capacityto form short contacts with neighboring residues. The dual ability of clamps to simultaneously form Watson−Crick and Hoogsteenhydrogen bonds offers a novel perspective on the effect of modifications on triplex stability, previously unexplored with triplexformingoligonucleotides (TFOs). Finally, the bis-pyrimidine clamps that formed the most stable parallel triplexes were applied in athermal lateral flow (TLF) sensing device, demonstrating their potential as biosensing probes. These clamps effectively detected thesynthetic DNA target with limits of detection (LoDs) ranging from 0.05 to 0.001 nM. Understanding the best modification strategiesand their impact on the triplex structure will advance the development of clamps as biosensing and therapeutic agents.American Chemical Society2026202620252026info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion14 p.application/pdfhttps://hdl.handle.net/2445/227188Articles publicats en revistes (Enginyeria Electrònica i Biomèdica)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1021/acsomega.5c02155ACS Omega, 2025, vol. 10, num.22, p. 23535-23548https://doi.org/10.1021/acsomega.5c02155cc-by (c) Domínguez, Arnau et al., 2024https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2271882026-05-29T05:05:01Z |
| dc.title.none.fl_str_mv |
Modified Bis-pyrimidine Clamps for Triplex Formation and Their Usein SARS-CoV‑2 Detection |
| title |
Modified Bis-pyrimidine Clamps for Triplex Formation and Their Usein SARS-CoV‑2 Detection |
| spellingShingle |
Modified Bis-pyrimidine Clamps for Triplex Formation and Their Usein SARS-CoV‑2 Detection Domínguez, Arnau Estructura química Genètica SARS-CoV-2 Chemical structure Genetics SARS-CoV-2 |
| title_short |
Modified Bis-pyrimidine Clamps for Triplex Formation and Their Usein SARS-CoV‑2 Detection |
| title_full |
Modified Bis-pyrimidine Clamps for Triplex Formation and Their Usein SARS-CoV‑2 Detection |
| title_fullStr |
Modified Bis-pyrimidine Clamps for Triplex Formation and Their Usein SARS-CoV‑2 Detection |
| title_full_unstemmed |
Modified Bis-pyrimidine Clamps for Triplex Formation and Their Usein SARS-CoV‑2 Detection |
| title_sort |
Modified Bis-pyrimidine Clamps for Triplex Formation and Their Usein SARS-CoV‑2 Detection |
| dc.creator.none.fl_str_mv |
Domínguez, Arnau Gargallo Gómez, Raimundo Cuestas-Ayllón, Carlos Gómez-Pinto, Irene Fàbrega, Carmen Martínez de la Fuente, Jesús Damha, M. J. González, Carlos Eritja i Casadellà, Ramon Aviñó Andrés, Anna |
| author |
Domínguez, Arnau |
| author_facet |
Domínguez, Arnau Gargallo Gómez, Raimundo Cuestas-Ayllón, Carlos Gómez-Pinto, Irene Fàbrega, Carmen Martínez de la Fuente, Jesús Damha, M. J. González, Carlos Eritja i Casadellà, Ramon Aviñó Andrés, Anna |
| author_role |
author |
| author2 |
Gargallo Gómez, Raimundo Cuestas-Ayllón, Carlos Gómez-Pinto, Irene Fàbrega, Carmen Martínez de la Fuente, Jesús Damha, M. J. González, Carlos Eritja i Casadellà, Ramon Aviñó Andrés, Anna |
| author2_role |
author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Estructura química Genètica SARS-CoV-2 Chemical structure Genetics SARS-CoV-2 |
| topic |
Estructura química Genètica SARS-CoV-2 Chemical structure Genetics SARS-CoV-2 |
| description |
The formation of nucleic acid triple helices (“triplexes”) is an area of great interest due to their potential role in thenatural and artificial regulation of gene expression or for use in analytical, diagnostic, or synthetic methods. During the coronaviruspandemic, a large search for novel methods for the detection of SARS-CoV-2 was undertaken. Based on triplex affinity capture andusing polypurine reverse-Hoogsteen hairpins, a method known as Triplex Enhanced Nucleic Acid Detection Assay (TENADA) wasdeveloped for the rapid detection of SARS-CoV-2 without the need for polymerase chain reaction (PCR) amplification. In this work,to expand the targeting scope of this method, we explored triplex-forming bis-pyrimidine clamps targeting a polypurine sequence inthe ORF1a region of SARS-CoV-2. To enhance parallel triplex stability, 2′-sugar and 5-methylpyrimidine modifications wereincorporated into both strands of the clamps, and their effect on the triplexes formed was assessed via NMR and other biophysicalmethods. The results revealed distinct stabilizing effects of the modifications, influenced by their size, sugar puckering, and capacityto form short contacts with neighboring residues. The dual ability of clamps to simultaneously form Watson−Crick and Hoogsteenhydrogen bonds offers a novel perspective on the effect of modifications on triplex stability, previously unexplored with triplexformingoligonucleotides (TFOs). Finally, the bis-pyrimidine clamps that formed the most stable parallel triplexes were applied in athermal lateral flow (TLF) sensing device, demonstrating their potential as biosensing probes. These clamps effectively detected thesynthetic DNA target with limits of detection (LoDs) ranging from 0.05 to 0.001 nM. Understanding the best modification strategiesand their impact on the triplex structure will advance the development of clamps as biosensing and therapeutic agents. |
| publishDate |
2025 |
| dc.date.none.fl_str_mv |
2025 2026 2026 2026 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/227188 |
| url |
https://hdl.handle.net/2445/227188 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Reproducció del document publicat a: https://doi.org/10.1021/acsomega.5c02155 ACS Omega, 2025, vol. 10, num.22, p. 23535-23548 https://doi.org/10.1021/acsomega.5c02155 |
| dc.rights.none.fl_str_mv |
cc-by (c) Domínguez, Arnau et al., 2024 https://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
cc-by (c) Domínguez, Arnau et al., 2024 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
| dc.format.none.fl_str_mv |
14 p. application/pdf |
| dc.publisher.none.fl_str_mv |
American Chemical Society |
| publisher.none.fl_str_mv |
American Chemical Society |
| dc.source.none.fl_str_mv |
Articles publicats en revistes (Enginyeria Electrònica i Biomèdica) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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