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A new noncanonical anionic peptide that translocates a cellular blood-brain barrier model

dc.contributor.authorNeves Coelho, Sara
dc.contributor.authorEleutério, Rute P.
dc.contributor.authorEnguita, Francisco J.
dc.contributor.authorNeves, Vera
dc.contributor.authorCastanho, Miguel A. R. B.
dc.date.accessioned2018-04-02T14:47:34Z
dc.date.available2018-04-02T14:47:34Z
dc.date.issued2017
dc.description© 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).pt_PT
dc.description.abstractThe capacity to transport therapeutic molecules across the blood–brain barrier (BBB) represents a breakthrough in the development of tools for the treatment of many central nervous system (CNS)-associated diseases. The BBB, while being protective against infectious agents, hinders the brain uptake of many drugs. Hence, finding safe shuttles able to overcome the BBB is of utmost importance. Herein, we identify a new BBB-translocating peptide with unique properties. For years it was thought that cationic sequences were mandatory for a cell-penetrating peptide (CPP) to achieve cellular internalization. Despite being anionic at physiological pH, PepNeg (sequence (SGTQEEY) is an efficient BBB translocator that is able to carry a large cargo (27 kDa), while maintaining BBB integrity. In addition, PepNeg is able to use two distinct methods of translocation, energy-dependent and -independent, suggesting that direct penetration might occur when low concentrations of peptide are presented to cells. The discovery of this new anionic trans-BBB peptide allows the development of new delivery systems to the CNS and contributes to the need to rethink the role of electrostatic attraction in BBB-translocationpt_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; PTDC/BBBNAN/1578/2014) and Marie Sklodowska-Curie Research and Innovation Staff Exchange (MSCA-RISE), call 20-MSCA-RISE-2014 (grant agreement H20 644167—INPACT).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationMolecules 2017, 22, 1753pt_PT
dc.identifier.doidoi:10.3390/molecules22101753pt_PT
dc.identifier.issn1420-3049
dc.identifier.urihttp://hdl.handle.net/10451/32538
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationPTDC/BBBNAN/1578/2014pt_PT
dc.relationPeptides for blood-brain barrier transmigration and drug delivery - novel therapies for the central nervous system CNS
dc.relation.publisherversionhttp://www.mdpi.com/journal/moleculespt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectCell-penetrating peptidept_PT
dc.subjectBlood–brain barrierpt_PT
dc.subjectAnionic peptidept_PT
dc.subjectDrug-delivery systemspt_PT
dc.titleA new noncanonical anionic peptide that translocates a cellular blood-brain barrier modelpt_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.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F94466%2F2013/PT
oaire.citation.issue10pt_PT
oaire.citation.titleMoleculespt_PT
oaire.citation.volume22pt_PT
person.familyNameNeves Coelho
person.givenNameSara
person.identifier.orcid0000-0003-2411-833X
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationb32d580c-c51b-4d9a-9b1b-401116f02e1a
relation.isAuthorOfPublication.latestForDiscoveryb32d580c-c51b-4d9a-9b1b-401116f02e1a
relation.isProjectOfPublication4b808757-8ecf-4878-8587-418aa9007bfb
relation.isProjectOfPublication.latestForDiscovery4b808757-8ecf-4878-8587-418aa9007bfb

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