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Highly selective capture of minicircle DNA biopharmaceuticals by a novel zinc-histidine peptide conjugate

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Resumo:The use of minicircle DNA (mcDNA) biomolecules as a pharmaceutical product holds remarkable potential due to their improved therapeutic efficacy in comparison with standard non-viral gene expression vectors. However, mcDNA translation into clinical application is still highly restricted due to the lack of robust technologies for minicircles detection and purification. In this study, the potential of a zinc-binding histidine-based peptide to function as a novel ligand for mcDNA recovery was investigated by using high-throughput surface plasmon resonance (SPR) analysis. The histidine-based peptide successfully bound zinc cationic ions and had affinity towards mcDNA biomolecules as confirmed by the dynamic binding responses obtained in SPR experiments. Notably, the obtained results indicate that not only zinc-peptide ligands are able to bind mcDNA with very high affinity (KD = 4.21 × 10−10 M), but also that this interaction is mostly dependent on buffer type. In general, the findings indicated that Zn2+ bound peptide has high affinity to mcDNA in low ionic strength buffers, whereas with high salt buffers no binding is detected. Overall, the novel zinc-binding peptide has shown to have suitable properties for mcDNA binding and recovery under experimental conditions that assure genetic material stability. More importantly, the straightforward approach of employing simple biomimetic ligands for mcDNA capture will contribute for development of new technologies to purify DNA biopharmaceuticals.
Autores principais:Gaspar, Vítor Manuel Abreu
Outros Autores:Cruz, Carla Patrícia Alves Freire Madeira; Queiroz, João; Pichon, Chantal; Correia, Ilídio; Sousa, Fani
Assunto:Minicircle DNA Affinity interactions Biopharmaceuticals Biomimetic peptide
Ano:2016
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso restrito
Instituição associada:Universidade da Beira Interior
Idioma:inglês
Origem:uBibliorum
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author Gaspar, Vítor Manuel Abreu
author2 Cruz, Carla Patrícia Alves Freire Madeira
Queiroz, João
Pichon, Chantal
Correia, Ilídio
Sousa, Fani
author2_role author
author
author
author
author
author_facet Gaspar, Vítor Manuel Abreu
Cruz, Carla Patrícia Alves Freire Madeira
Queiroz, João
Pichon, Chantal
Correia, Ilídio
Sousa, Fani
author_role author
contributor_name_str_mv uBibliorum
country_str PT
creators_json_txt [{\"Person.name\":\"Gaspar, Vítor Manuel Abreu\",\"Person.identifier.orcid\":\"0000-0002-0372-2493\"},{\"Person.name\":\"Cruz, Carla Patrícia Alves Freire Madeira\"},{\"Person.name\":\"Queiroz, João\",\"Person.identifier.orcid\":\"0000-0002-3096-8325\"},{\"Person.name\":\"Pichon, Chantal\"},{\"Person.name\":\"Correia, Ilídio\",\"Person.identifier.orcid\":\"0000-0003-1613-9675\"},{\"Person.name\":\"Sousa, Fani\",\"Person.identifier.orcid\":\"0000-0001-9996-2194\"}]
datacite.contributors.contributor.contributorName.fl_str_mv uBibliorum
datacite.creators.creator.creatorName.fl_str_mv Gaspar, Vítor Manuel Abreu
Cruz, Carla Patrícia Alves Freire Madeira
Queiroz, João
Pichon, Chantal
Correia, Ilídio
Sousa, Fani
datacite.date.Accepted.fl_str_mv 2016-10-31T00:00:00Z
datacite.date.available.fl_str_mv 2018-03-22T08:45:52Z
datacite.date.embargoed.fl_str_mv 2018-03-22T08:45:52Z
datacite.rights.fl_str_mv http://purl.org/coar/access_right/c_16ec
datacite.subjects.subject.fl_str_mv Minicircle DNA
Affinity interactions
Biopharmaceuticals
Biomimetic peptide
datacite.titles.title.fl_str_mv Highly selective capture of minicircle DNA biopharmaceuticals by a novel zinc-histidine peptide conjugate
dc.contributor.none.fl_str_mv uBibliorum
dc.creator.none.fl_str_mv Gaspar, Vítor Manuel Abreu
Cruz, Carla Patrícia Alves Freire Madeira
Queiroz, João
Pichon, Chantal
Correia, Ilídio
Sousa, Fani
dc.date.Accepted.fl_str_mv 2016-10-31T00:00:00Z
dc.date.available.fl_str_mv 2018-03-22T08:45:52Z
dc.date.embargoed.fl_str_mv 2018-03-22T08:45:52Z
dc.format.none.fl_str_mv application/pdf
dc.identifier.none.fl_str_mv http://hdl.handle.net/10400.6/4693
dc.language.none.fl_str_mv eng
dc.publisher.none.fl_str_mv Elsevier
dc.rights.none.fl_str_mv http://purl.org/coar/access_right/c_16ec
dc.subject.none.fl_str_mv Minicircle DNA
Affinity interactions
Biopharmaceuticals
Biomimetic peptide
dc.title.fl_str_mv Highly selective capture of minicircle DNA biopharmaceuticals by a novel zinc-histidine peptide conjugate
dc.type.none.fl_str_mv http://purl.org/coar/resource_type/c_6501
description The use of minicircle DNA (mcDNA) biomolecules as a pharmaceutical product holds remarkable potential due to their improved therapeutic efficacy in comparison with standard non-viral gene expression vectors. However, mcDNA translation into clinical application is still highly restricted due to the lack of robust technologies for minicircles detection and purification. In this study, the potential of a zinc-binding histidine-based peptide to function as a novel ligand for mcDNA recovery was investigated by using high-throughput surface plasmon resonance (SPR) analysis. The histidine-based peptide successfully bound zinc cationic ions and had affinity towards mcDNA biomolecules as confirmed by the dynamic binding responses obtained in SPR experiments. Notably, the obtained results indicate that not only zinc-peptide ligands are able to bind mcDNA with very high affinity (KD = 4.21 × 10−10 M), but also that this interaction is mostly dependent on buffer type. In general, the findings indicated that Zn2+ bound peptide has high affinity to mcDNA in low ionic strength buffers, whereas with high salt buffers no binding is detected. Overall, the novel zinc-binding peptide has shown to have suitable properties for mcDNA binding and recovery under experimental conditions that assure genetic material stability. More importantly, the straightforward approach of employing simple biomimetic ligands for mcDNA capture will contribute for development of new technologies to purify DNA biopharmaceuticals.
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funding.funder.alternateName_str_mv FCT
FCT
FCT
funding.funder.identifier_str_mv http://doi.org/10.13039/501100001871
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funding.funder.name_str_mv Fundação para a Ciência e a Tecnologia
Fundação para a Ciência e a Tecnologia
Fundação para a Ciência e a Tecnologia
funding.identifier_str_mv PEst-C/SAU/UI0709/2011
EXPL/QEQ-MED/1068/2013
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funding.name_str_mv 6820 - DCRRNI ID
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Bolsa de Pós-Doutoramento
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EXPL/QEQ-MED/1068/2013
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SFRH/BPD/100015/2014
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instname_str Universidade da Beira Interior
language eng
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oai_identifier_str oai:ubibliorum.ubi.pt:10400.6/4693
organization_str_mv urn:organizationAcronym:ubi
person_str_mv Gaspar, Vítor Manuel Abreu
Gaspar, Vítor Manuel Abreu
https://www.ciencia-id.pt/6F16-3640-73E3
6F16-3640-73E3
http://orcid.org/0000-0002-0372-2493
0000-0002-0372-2493
Cruz, Carla Patrícia Alves Freire Madeira
Queiroz, João
Queiroz, João
https://www.ciencia-id.pt/931E-B66D-E341
931E-B66D-E341
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Pichon, Chantal
Correia, Ilídio
Correia, Ilídio
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Sousa, Fani
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publishDate 2016
publisher.none.fl_str_mv Elsevier
reponame_str uBibliorum
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spelling engElsevierpt_PTThe use of minicircle DNA (mcDNA) biomolecules as a pharmaceutical product holds remarkable potential due to their improved therapeutic efficacy in comparison with standard non-viral gene expression vectors. However, mcDNA translation into clinical application is still highly restricted due to the lack of robust technologies for minicircles detection and purification. In this study, the potential of a zinc-binding histidine-based peptide to function as a novel ligand for mcDNA recovery was investigated by using high-throughput surface plasmon resonance (SPR) analysis. The histidine-based peptide successfully bound zinc cationic ions and had affinity towards mcDNA biomolecules as confirmed by the dynamic binding responses obtained in SPR experiments. Notably, the obtained results indicate that not only zinc-peptide ligands are able to bind mcDNA with very high affinity (KD = 4.21 × 10−10 M), but also that this interaction is mostly dependent on buffer type. In general, the findings indicated that Zn2+ bound peptide has high affinity to mcDNA in low ionic strength buffers, whereas with high salt buffers no binding is detected. Overall, the novel zinc-binding peptide has shown to have suitable properties for mcDNA binding and recovery under experimental conditions that assure genetic material stability. More importantly, the straightforward approach of employing simple biomimetic ligands for mcDNA capture will contribute for development of new technologies to purify DNA biopharmaceuticals.application/pdfpt_PTHighly selective capture of minicircle DNA biopharmaceuticals by a novel zinc-histidine peptide conjugatePersonalGaspar, Vítor Manuel AbreuDSpacehttp://dspace.org/items/3eeac15e-ebf4-4dc2-aeb8-698087d6d2fcDSpacehttp://dspace.org/items/3eeac15e-ebf4-4dc2-aeb8-698087d6d2fcGasparVítorCiência IDhttps://www.ciencia-id.pt6F16-3640-73E3ORCIDhttp://orcid.org0000-0002-0372-2493Researcher IDhttps://www.researcherid.comB-1602-2017Scopus Author IDhttps://www.scopus.com36968590900Cruz, Carla Patrícia Alves Freire MadeiraPersonalQueiroz, JoãoDSpacehttp://dspace.org/items/c798c033-c160-4f99-a8ad-04416923943fDSpacehttp://dspace.org/items/c798c033-c160-4f99-a8ad-04416923943fQueirozJoãoCiência IDhttps://www.ciencia-id.pt931E-B66D-E341ORCIDhttp://orcid.org0000-0002-3096-8325Researcher IDhttps://www.researcherid.comL-3104-2014Scopus Author IDhttps://www.scopus.com7003705645Pichon, ChantalPersonalCorreia, IlídioDSpacehttp://dspace.org/items/f2c3e779-34a2-4309-950a-80687664c6adDSpacehttp://dspace.org/items/f2c3e779-34a2-4309-950a-80687664c6adCorreiaIlídio Joaquim SobreiraCiência IDhttps://www.ciencia-id.ptF610-7373-DC81ORCIDhttp://orcid.org0000-0003-1613-9675Scopus Author IDhttps://www.scopus.com7003557499PersonalSousa, FaniDSpacehttp://dspace.org/items/2935de97-fc90-4d38-9505-4caa364f8a10DSpacehttp://dspace.org/items/2935de97-fc90-4d38-9505-4caa364f8a10SousaFaniCiência IDhttps://www.ciencia-id.pt991D-2E13-A840ORCIDhttp://orcid.org0000-0001-9996-2194Researcher IDhttps://www.researcherid.comA-2014-2017Scopus Author IDhttps://www.scopus.com7005110268HostingInstitutionOrganizationaluBibliorume-mailmailto:noreplyuBibliorum@ubi.ptnoreplyuBibliorum@ubi.ptDOIIsPartOf10.1016/j.seppur.2016.10.0542018-03-22T08:45:52Z2016-10-312016-10-31T00:00:00ZHandlehttp://hdl.handle.net/10400.6/4693http://purl.org/coar/access_right/c_16ecrestricted accessMinicircle DNAAffinity interactionsBiopharmaceuticalsBiomimetic peptide1582020 bytesFundação para a Ciência e a TecnologiaStrategic Project - UI 709 - 2011-2012 [PEst-C/SAU/UI0709/2011]info:eu-repo/grantAgreement/FCT/6820 - DCRRNI ID/PEst-C%2FSAU%2FUI0709%2F2011/PTPEst-C/SAU/UI0709/20116820 - DCRRNI IDCrossref Funder IDhttp://doi.org/10.13039/501100001871Fundação para a Ciência e a TecnologiaG-quadruplex binders for cancer therapy [EXPL/QEQ-MED/1068/2013]info:eu-repo/grantAgreement/FCT/5876-PPCDTI/EXPL%2FQEQ-MED%2F1068%2F2013/PTEXPL/QEQ-MED/1068/20135876-PPCDTICrossref Funder IDhttp://doi.org/10.13039/501100001871Fundação para a Ciência e a TecnologiaBolsa de Pós-Doutoramento FCT: Purification, detection and stabilization of G-quadruplex for cancer therapy [SFRH/BPD/100015/2014]info:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F100015%2F2014/PTSFRH/BPD/100015/2014Bolsa de Pós-DoutoramentoCrossref Funder IDhttp://doi.org/10.13039/501100001871literaturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_16ecapplication/pdffulltexthttps://ubibliorum.ubi.pt/bitstreams/83c2238f-5a04-4f3a-930e-d0c3fe06b5da/downloadSeparation and Purification Technology174417424
spellingShingle Highly selective capture of minicircle DNA biopharmaceuticals by a novel zinc-histidine peptide conjugate
Gaspar, Vítor Manuel Abreu
Minicircle DNA
Affinity interactions
Biopharmaceuticals
Biomimetic peptide
status SINGLETON
subject.fl_str_mv Minicircle DNA
Affinity interactions
Biopharmaceuticals
Biomimetic peptide
title Highly selective capture of minicircle DNA biopharmaceuticals by a novel zinc-histidine peptide conjugate
title_full Highly selective capture of minicircle DNA biopharmaceuticals by a novel zinc-histidine peptide conjugate
title_fullStr Highly selective capture of minicircle DNA biopharmaceuticals by a novel zinc-histidine peptide conjugate
title_full_unstemmed Highly selective capture of minicircle DNA biopharmaceuticals by a novel zinc-histidine peptide conjugate
title_short Highly selective capture of minicircle DNA biopharmaceuticals by a novel zinc-histidine peptide conjugate
title_sort Highly selective capture of minicircle DNA biopharmaceuticals by a novel zinc-histidine peptide conjugate
topic Minicircle DNA
Affinity interactions
Biopharmaceuticals
Biomimetic peptide
topic_facet Minicircle DNA
Affinity interactions
Biopharmaceuticals
Biomimetic peptide
url http://hdl.handle.net/10400.6/4693
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