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

Detalhes bibliográficos
Autor(a) principal: Cavaco, Marco
Data de Publicação: 2021
Outros Autores: Frutos, Silvia, Oliete, Paula, Valle, Javier, Andreu, David, Castanho, Miguel A. R. B., Vila-Perelló, Miquel, Neves, Vera
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/57420
Resumo: © 2021 The Authors. Published by American Chemical Society
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spelling Conjugation of a blood brain barrier peptide shuttle to an Fc domain for brain delivery of therapeutic biomoleculesAntibody fragmentsBBB peptide shuttleBrain disordersSite-specific conjugationStreamlined expressed protein ligation© 2021 The Authors. Published by American Chemical SocietyThe 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.We 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.American Chemical SocietyRepositório da Universidade de LisboaCavaco, MarcoFrutos, SilviaOliete, PaulaValle, JavierAndreu, DavidCastanho, Miguel A. R. B.Vila-Perelló, MiquelNeves, Vera2023-05-15T11:45:07Z20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/57420engACS Med. Chem. Lett. 2021, 12, 1663−16681948-587510.1021/acsmedchemlett.1c00225info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T17:05:40Zoai:repositorio.ul.pt:10451/57420Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:07:50.469786Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Conjugation of a blood brain barrier peptide shuttle to an Fc domain for brain delivery of therapeutic biomolecules
title Conjugation of a blood brain barrier peptide shuttle to an Fc domain for brain delivery of therapeutic biomolecules
spellingShingle Conjugation of a blood brain barrier peptide shuttle to an Fc domain for brain delivery of therapeutic biomolecules
Cavaco, Marco
Antibody fragments
BBB peptide shuttle
Brain disorders
Site-specific conjugation
Streamlined expressed protein ligation
title_short Conjugation of a blood brain barrier peptide shuttle to an Fc domain for brain delivery of therapeutic biomolecules
title_full Conjugation of a blood brain barrier peptide shuttle to an Fc domain for brain delivery of therapeutic biomolecules
title_fullStr Conjugation of a blood brain barrier peptide shuttle to an Fc domain for brain delivery of therapeutic biomolecules
title_full_unstemmed Conjugation of a blood brain barrier peptide shuttle to an Fc domain for brain delivery of therapeutic biomolecules
title_sort Conjugation of a blood brain barrier peptide shuttle to an Fc domain for brain delivery of therapeutic biomolecules
author Cavaco, Marco
author_facet Cavaco, Marco
Frutos, Silvia
Oliete, Paula
Valle, Javier
Andreu, David
Castanho, Miguel A. R. B.
Vila-Perelló, Miquel
Neves, Vera
author_role author
author2 Frutos, Silvia
Oliete, Paula
Valle, Javier
Andreu, David
Castanho, Miguel A. R. B.
Vila-Perelló, Miquel
Neves, Vera
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Cavaco, Marco
Frutos, Silvia
Oliete, Paula
Valle, Javier
Andreu, David
Castanho, Miguel A. R. B.
Vila-Perelló, Miquel
Neves, Vera
dc.subject.por.fl_str_mv Antibody fragments
BBB peptide shuttle
Brain disorders
Site-specific conjugation
Streamlined expressed protein ligation
topic Antibody fragments
BBB peptide shuttle
Brain disorders
Site-specific conjugation
Streamlined expressed protein ligation
description © 2021 The Authors. Published by American Chemical Society
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-01-01T00:00:00Z
2023-05-15T11:45:07Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/57420
url http://hdl.handle.net/10451/57420
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv ACS Med. Chem. Lett. 2021, 12, 1663−1668
1948-5875
10.1021/acsmedchemlett.1c00225
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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