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Conjugation of a blood brain barrier peptide shuttle to an Fc domain for brain delivery of therapeutic biomolecules

2021Artigo científico Acesso aberto
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dc.contributor.authorCavaco, Marco
dc.contributor.authorFrutos, Silvia
dc.contributor.authorOliete, Paula
dc.contributor.authorValle, Javier
dc.contributor.authorAndreu, David
dc.contributor.authorCastanho, Miguel A. R. B.
dc.contributor.authorVila-Perelló, Miquel
dc.contributor.authorNeves, Vera
dc.date.accessioned2023-05-15T11:45:07Z
dc.date.available2023-05-15T11:45:07Z
dc.date.issued2021
dc.description© 2021 The Authors. Published by American Chemical Societypt_PT
dc.description.abstractThe frequency of brain disease has increased significantly in the past years. After diagnosis, therapeutic options are usually limited, which demands the development of innovative therapeutic strategies. The use of antibody−drug conjugates (ADCs) is promising but highly limited by the existence of the blood−brain barrier (BBB). To overcome the impermeability of this barrier, antibody fragments can be engineered and conjugated to BBB peptide shuttles (BBBpS), which are capable of brain penetration. Herein, we linked the highly efficient BBBpS, PepH3, to the IgG fragment crystallizable (Fc) domain using the streamlined expressed protein ligation (SEPL) method. With this strategy, we obtained an Fc-PepH3 scaffold that can carry different payloads. Fc-PepH3 was shown to be nontoxic, capable of crossing an in vitro cellular BBB model, and able to bind to the neonatal Fc receptor (FcRn), which is responsible for antibody long half-life (t1/2). Overall, we demonstrated the potential of Fc-PepH3 as a versatile platform readily adaptable to diverse drugs of therapeutic value to treat different brain conditions.pt_PT
dc.description.sponsorshipWe acknowledge the Portuguese Funding Agency, Fundação para a Ciência e a Tecnologia, FCT IP (Grant Nos. PD/BD/128281/2017, PTDC/BIA-BQM/5027/2020, and DL 57/2016/CP1451/CT0023), and “la Caixa” Banking Foundation (ID 100010434), under the agreement LCF/PR/HR17/5215001.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationACS Med. Chem. Lett. 2021, 12, 1663−1668pt_PT
dc.identifier.doi10.1021/acsmedchemlett.1c00225pt_PT
dc.identifier.issn1948-5875
dc.identifier.urihttp://hdl.handle.net/10451/57420
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherAmerican Chemical Societypt_PT
dc.relationPD/BD/128281/2017pt_PT
dc.relationNot Available
dc.relation.publisherversionhttps://pubs.acs.org/journal/amclctpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectAntibody fragmentspt_PT
dc.subjectBBB peptide shuttlept_PT
dc.subjectBrain disorderspt_PT
dc.subjectSite-specific conjugationpt_PT
dc.subjectStreamlined expressed protein ligationpt_PT
dc.titleConjugation of a blood brain barrier peptide shuttle to an Fc domain for brain delivery of therapeutic biomoleculespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleNot Available
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBIA-BQM%2F5027%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/DL 57%2F2016/DL 57%2F2016%2FCP1451%2FCT0023/PT
oaire.citation.endPage1668pt_PT
oaire.citation.issue11pt_PT
oaire.citation.startPage1663pt_PT
oaire.citation.titleACS Medicinal Chemistry Letterspt_PT
oaire.citation.volume12pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStreamDL 57/2016
person.familyNameCavaco
person.familyNameCastanho
person.familyNameNeves
person.givenNameMarco
person.givenNameMiguel
person.givenNameVera
person.identifier1069324
person.identifier953259
person.identifier.ciencia-id1412-63B8-7494
person.identifier.ciencia-id671C-1860-A160
person.identifier.orcid0000-0002-0938-9038
person.identifier.orcid0000-0001-7891-7562
person.identifier.orcid0000-0002-2989-7208
person.identifier.ridO-2176-2018
person.identifier.scopus-author-id56605575600
person.identifier.scopus-author-id26537945300
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
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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relation.isAuthorOfPublication.latestForDiscoveryf5e46f85-fabf-450a-9ee2-1c7b59410892
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