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Novel peptides derived from dengue virus capsid protein translocate reversibly the blood−brain barrier through a receptor-free mechanism

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dc.contributor.authorNeves, Vera
dc.contributor.authorSilva, Frederico Aires da
dc.contributor.authorMorais, Maurício
dc.contributor.authorGano, Lurdes
dc.contributor.authorRibeiro, Elisabete
dc.contributor.authorPinto, Antónia
dc.contributor.authorAguiar, Sandra
dc.contributor.authorGaspar, Diana
dc.contributor.authorFernandes, Célia
dc.contributor.authorCorreia, João D. G.
dc.contributor.authorCastanho, Miguel A. R. B.
dc.date.accessioned2018-04-16T13:09:06Z
dc.date.available2018-04-16T13:09:06Z
dc.date.issued2017
dc.description© 2017 American Chemical Societypt_PT
dc.description.abstractThe delivery of therapeutic molecules to the central nervous system is hampered by poor delivery across the blood-brain barrier (BBB). Several strategies have been proposed to enhance transport into the brain, including invasive techniques and receptor-mediated transport (RMT). Both approaches have several drawbacks, such as BBB disruption, receptor saturation, and off-target effects, raising safety issues. Herein, we show that specific domains of Dengue virus type 2 capsid protein (DEN2C) can be used as trans-BBB peptide vectors. Their mechanism of translocation is receptor-independent and consistent with adsorptive-mediated transport (AMT). One peptide in particular, named PepH3, reaches equilibrium distribution concentrations across the BBB in less than 24 h in a cellular in vitro assay. Importantly, in vivo biodistribution data with radiolabeled peptide derivatives show high brain penetration. In addition, there is fast clearance from the brain and high levels of excretion, showing that PepH3 is a very good candidate to be used as a peptide shuttle taking cargo in and out of the brain.pt_PT
dc.description.sponsorshipThe authors thank the Portuguese Funding Agency, Fundação para a Ciência e a Tecnologia, FCT IP, for financial support (grants SFRH/BPD/94466/2013; SFRH/BPD/109010/2015; IF/01010/2013; PTDC/BBBNAN/1578/2014; HIVERA/ 0002/2013) and Marie Skłodowska-Curie Research and Innovation Staff Exchange (MSCA-RISE), call 20-MSCARISE-2014 (grant agreement H20 644167 − INPACT). M.M., L.G., C.F., and J.D.G.C. gratefully acknowledge FCT support through the UID/Multi/04349/2013 project.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationACS Chem. Biol. 2017, 12, 1257−1268pt_PT
dc.identifier.doi10.1021/acschembio.7b00087pt_PT
dc.identifier.issn1554-8929
dc.identifier.urihttp://hdl.handle.net/10451/32811
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherAmerican Chemical Societypt_PT
dc.relationIF/01010/2013pt_PT
dc.relationPeptides for blood-brain barrier transmigration and drug delivery - novel therapies for the central nervous system CNS
dc.relationCell-cell direct/indirect communication in metastatic breast cancer as a control point in oncotherapy
dc.relationCentre for Nuclear Sciences and Technologies
dc.relation.publisherversionhttps://pubs.acs.org/journal/acbcctpt_PT
dc.titleNovel peptides derived from dengue virus capsid protein translocate reversibly the blood−brain barrier through a receptor-free mechanismpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitlePeptides for blood-brain barrier transmigration and drug delivery - novel therapies for the central nervous system CNS
oaire.awardTitleCell-cell direct/indirect communication in metastatic breast cancer as a control point in oncotherapy
oaire.awardTitleCentre for Nuclear Sciences and Technologies
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F94466%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F109010%2F2015/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FMulti%2F04349%2F2013/PT
oaire.citation.endPage1268pt_PT
oaire.citation.issue5pt_PT
oaire.citation.startPage1257pt_PT
oaire.citation.titleACS Chemical Biologypt_PT
oaire.citation.volume12pt_PT
oaire.fundingStream6817 - DCRRNI ID
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication4b808757-8ecf-4878-8587-418aa9007bfb
relation.isProjectOfPublication0ec23e32-e1a5-4681-9cb6-491aae58a6de
relation.isProjectOfPublicationf466786c-bc57-4dea-9e91-af46d9d86d93
relation.isProjectOfPublication.latestForDiscovery0ec23e32-e1a5-4681-9cb6-491aae58a6de

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