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

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• dc.contributor.author Cavaco, Marco
• dc.contributor.author Frutos, Silvia
• dc.contributor.author Oliete, Paula
• dc.contributor.author Valle, Javier
• dc.contributor.author Andreu Martínez, David
• dc.contributor.author Castanho, Miguel A.R.B.
• dc.contributor.author Vila-Perelló, Miquel
• dc.contributor.author Neves, Vera
• dc.date.accessioned 2023-03-22T07:13:33Z
• dc.date.available 2023-03-22T07:13:33Z
• dc.date.issued 2021
• dc.description.abstract The 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 (t 1/2). 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.
• dc.format.mimetype application/pdf
• dc.identifier.citation Cavaco M, Frutos S, Oliete P, Valle J, Andreu D, Castanho Miguel A.R.B., Vila-Perelló M, Neves V. Conjugation of a blood brain barrier peptide shuttle to an Fc domain for brain delivery of therapeutic biomolecules. ACS Med Chem Lett. 2021 Sep 2;12(11):1663-8. DOI: 10.1021/acsmedchemlett.1c00225
• dc.identifier.doi http://dx.doi.org/10.1021/acsmedchemlett.1c00225
• dc.identifier.issn 1948-5875
• dc.identifier.uri http://hdl.handle.net/10230/56312
• dc.language.iso eng
• dc.publisher American Chemical Society (ACS)
• dc.relation.ispartof ACS Med Chem Lett. 2021 Sep 2;12(11):1663-8
• dc.rights © 2021 The Authors. Published by American Chemical Society. This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/)
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Antibody fragments
• dc.subject.keyword BBB peptide shuttle
• dc.subject.keyword Brain disorders
• dc.subject.keyword Site-specific conjugation
• dc.subject.keyword Streamlined expressed protein ligation
• dc.title Conjugation of a blood brain barrier peptide shuttle to an Fc domain for brain delivery of therapeutic biomolecules
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion