Aptamer-peptide conjugates as a new strategy to modulate human α-thrombin binding affinity

Aptamers are single-stranded RNA or DNA molecules that specifically recognize their targets and have proven valuable for functionalizing sensitive biosensors. α-thrombin is a trypsin-like serine proteinase which plays a crucial role in haemostasis and thrombosis. An abnormal activity or overexpressi...

Descripción completa

Detalles Bibliográficos
Autores: Aviñó, Anna, Jorge, Andreia F., Huertas, César S., Cova, Tânia F.G.G., Pais, Alberto, Lechuga, Laura M., Eritja Casadellà, Ramón, Fàbrega, Carme
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2019
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/187428
Acceso en línea:http://hdl.handle.net/10261/187428
Access Level:acceso abierto
Palabra clave:Biosensors
Thrombin
Inhibition
Binding affinity
Aptamer-peptide conjugate
id ES_766d7f096f0340eede1f8ca03e04ee80
oai_identifier_str oai:digital.csic.es:10261/187428
network_acronym_str ES
network_name_str España
repository_id_str
spelling Aptamer-peptide conjugates as a new strategy to modulate human α-thrombin binding affinityAviñó, AnnaJorge, Andreia F.Huertas, César S.Cova, Tânia F.G.G.Pais, AlbertoLechuga, Laura M.Eritja Casadellà, RamónFàbrega, CarmeBiosensorsThrombinInhibitionBinding affinityAptamer-peptide conjugateAptamers are single-stranded RNA or DNA molecules that specifically recognize their targets and have proven valuable for functionalizing sensitive biosensors. α-thrombin is a trypsin-like serine proteinase which plays a crucial role in haemostasis and thrombosis. An abnormal activity or overexpression of this protein is associated with a variety of diseases. A great deal of attention was devoted to the construction of high-throughput biosensors for accurately detect thrombin for the early diagnosis and treatment of related diseases. Herein, we propose a new approach to modulate the interaction between α-thrombin and the aptamer TBA15. To this end, TBA15 was chemically conjugated to two peptide sequences (TBA-G3FIE-Ac and TBA-G3EIF-Ac) corresponding to a short fragment of the acidic region of the human factor V, which is known to interact directly with exosite I. Surface Plasmon Resonance (SPR) results showed enhanced analytical performances of thrombin with TBA-G3EIF-Ac than with TBA wild-type, reaching a limit of detection as low as 44.9 pM. Electrophoresis mobility shift assay (EMSA) corroborated the SPR results. Molecular dynamics (MD) simulations support experimental evidences and provided further insight into thrombin/TBA-peptide interaction. Our findings demonstrate that the combination of TBA15 with key interacting peptides offers good opportunities to produce sensitive devices for thrombin detection and potential candidates to block thrombin activity.The authors acknowledge the Laboratory for Advanced Computing at the University of Coimbra for providing {HPC, computing, consulting} resources that have contributed to the research results reported within this paper (URL http://www.lca.uc.pt). CIBER-BBN is an initiative funded by the VI National R + D + I Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program; The Instituto de Salud Carlos III with assistance from the European Regional Development and NANBIOSIS.Peer reviewedElsevierAviñó, Anna [0000-0003-3047-738X]Eritja Casadellà, Ramón [0000-0001-5383-9334]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201920192019info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/187428reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.1016/j.bbagen.2019.06.014Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1874282026-05-22T06:33:51Z
dc.title.none.fl_str_mv Aptamer-peptide conjugates as a new strategy to modulate human α-thrombin binding affinity
title Aptamer-peptide conjugates as a new strategy to modulate human α-thrombin binding affinity
spellingShingle Aptamer-peptide conjugates as a new strategy to modulate human α-thrombin binding affinity
Aviñó, Anna
Biosensors
Thrombin
Inhibition
Binding affinity
Aptamer-peptide conjugate
title_short Aptamer-peptide conjugates as a new strategy to modulate human α-thrombin binding affinity
title_full Aptamer-peptide conjugates as a new strategy to modulate human α-thrombin binding affinity
title_fullStr Aptamer-peptide conjugates as a new strategy to modulate human α-thrombin binding affinity
title_full_unstemmed Aptamer-peptide conjugates as a new strategy to modulate human α-thrombin binding affinity
title_sort Aptamer-peptide conjugates as a new strategy to modulate human α-thrombin binding affinity
dc.creator.none.fl_str_mv Aviñó, Anna
Jorge, Andreia F.
Huertas, César S.
Cova, Tânia F.G.G.
Pais, Alberto
Lechuga, Laura M.
Eritja Casadellà, Ramón
Fàbrega, Carme
author Aviñó, Anna
author_facet Aviñó, Anna
Jorge, Andreia F.
Huertas, César S.
Cova, Tânia F.G.G.
Pais, Alberto
Lechuga, Laura M.
Eritja Casadellà, Ramón
Fàbrega, Carme
author_role author
author2 Jorge, Andreia F.
Huertas, César S.
Cova, Tânia F.G.G.
Pais, Alberto
Lechuga, Laura M.
Eritja Casadellà, Ramón
Fàbrega, Carme
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Aviñó, Anna [0000-0003-3047-738X]
Eritja Casadellà, Ramón [0000-0001-5383-9334]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Biosensors
Thrombin
Inhibition
Binding affinity
Aptamer-peptide conjugate
topic Biosensors
Thrombin
Inhibition
Binding affinity
Aptamer-peptide conjugate
description Aptamers are single-stranded RNA or DNA molecules that specifically recognize their targets and have proven valuable for functionalizing sensitive biosensors. α-thrombin is a trypsin-like serine proteinase which plays a crucial role in haemostasis and thrombosis. An abnormal activity or overexpression of this protein is associated with a variety of diseases. A great deal of attention was devoted to the construction of high-throughput biosensors for accurately detect thrombin for the early diagnosis and treatment of related diseases. Herein, we propose a new approach to modulate the interaction between α-thrombin and the aptamer TBA15. To this end, TBA15 was chemically conjugated to two peptide sequences (TBA-G3FIE-Ac and TBA-G3EIF-Ac) corresponding to a short fragment of the acidic region of the human factor V, which is known to interact directly with exosite I. Surface Plasmon Resonance (SPR) results showed enhanced analytical performances of thrombin with TBA-G3EIF-Ac than with TBA wild-type, reaching a limit of detection as low as 44.9 pM. Electrophoresis mobility shift assay (EMSA) corroborated the SPR results. Molecular dynamics (MD) simulations support experimental evidences and provided further insight into thrombin/TBA-peptide interaction. Our findings demonstrate that the combination of TBA15 with key interacting peptides offers good opportunities to produce sensitive devices for thrombin detection and potential candidates to block thrombin activity.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019
2019
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/10261/187428
url http://hdl.handle.net/10261/187428
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.1016/j.bbagen.2019.06.014
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869411050306142208
score 15.81155

Similares en LA Referencia