Molecular determinants for brain targeting by peptides: a meta-analysis approach with experimental validation

Mostra el registre complet Registre parcial de l'ítem

• dc.contributor.author Cavaco, Marco
• dc.contributor.author Fraga, Patrícia
• dc.contributor.author Valle, Javier
• dc.contributor.author Silva, Rúben D.M.
• dc.contributor.author Gano, Lurdes
• dc.contributor.author Correia, João D.G.
• dc.contributor.author Andreu Martínez, David
• dc.contributor.author Castanho, Miguel A.R.B.
• dc.contributor.author Neves, Vera
• dc.date.accessioned 2024-07-15T06:47:03Z
• dc.date.available 2024-07-15T06:47:03Z
• dc.date.issued 2024
• dc.description.abstract Blood-brain barrier (BBB) peptide-shuttles (BBBpS) are able to translocate the BBB and reach the brain. Despite the importance of brain targeting in pharmacology, BBBpS are poorly characterized. Currently, their development relies on the empiric assumption that cell-penetrating peptides (CPPs), with proven ability to traverse lipid membranes, will likewise behave as a BBBpS. The relationship between CPPs/BBBpS remains elusive and, to the best of our knowledge, has not hitherto been subject to thorough experimental scrutiny. In this work, we have identified/quantified the main physicochemical properties of BBBpS and then searched for CPPs with these properties, hence potential BBBpS. The specific features found for BBBpS are: (i) small size, (ii) none or few aromatic residues, (iii) hydrophobic, and (iv) slight cationic nature. Then, we selected the 10 scoring best in an ordinary least squares analysis, and tested them in vitro and in vivo. Overall, we identified the molecular determinants for brain targeting by peptides, devised a methodology that can be used to assist in the design of peptides with potential brain penetration from amino acid residue sequences, and found four new BBBpS within the CPP library.
• dc.description.sponsorship The project leading to these results have received funding from “la Caixa” Foundation (ID 100010434) and FCT, I.P under the agreement LCF/PR/HP21/52310015; ​​European Union’s Horizon 2020 research and innovation program under grant agreement No 952455; and “Fundação para a Ciência e Tecnologia” (FCT, Portugal) (grant: 2021.00895.CEECIND, PD/BD/128281/2017, PTDC/BTM-MAT/2472/2021, UIDB/04349/2020 and PTDC/QUI-OUT/3854/2021). Work at Pompeu Fabra University supported by the “María de Maeztu” Program for Units of Excellence in R&D (CEX2018-000792-M) developed by the Spanish Ministry of Economy and Competitiveness (MINECO).
• dc.format.mimetype application/pdf
• dc.identifier.citation Cavaco M, Fraga P, Valle J, Silva RDM, Gano L, Correia JDG, et al. Molecular determinants for brain targeting by peptides: a meta-analysis approach with experimental validation. Fluids Barriers CNS. 2024 May 27;21(1):45. DOI: 10.1186/s12987-024-00545-5
• dc.identifier.doi http://dx.doi.org/10.1186/s12987-024-00545-5
• dc.identifier.issn 2045-8118
• dc.identifier.uri http://hdl.handle.net/10230/60746
• dc.language.iso eng
• dc.publisher BioMed Central
• dc.relation.ispartof Fluids Barriers CNS. 2024 May 27;21(1):45
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/952455
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/CEX2018-000792-M
• dc.rights © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Blood–brain barrier (BBB)
• dc.subject.keyword Blood–brain barrier peptide shuttles (BBBpS)
• dc.subject.keyword Brain delivery
• dc.subject.keyword Cell-penetrating peptides (CPPs)
• dc.subject.keyword Neurological disorders
• dc.title Molecular determinants for brain targeting by peptides: a meta-analysis approach with experimental validation
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion