Acylation of the S4(13)-PV cell-penetrating peptide as a means of enhancing its capacity to mediate nucleic acid delivery: Relevance of peptide/lipid interactions

• Tipo: Artigo em Revista Científica Internacional
• Data: 2018

Autores

Morais, CM (Autor) Outra; Cardoso, AM (Autor) Outra; Cunha, PP (Autor) Outra; Aguiar, L (Autor) Outra; Nuno Vale (Autor) ICBAS; Lage, E (Autor) Outra; Pinheiro, M (Autor) Outra; Nunes, C (Autor) Outra; Paula Gomes (Autor) FCUP; Salette Reis (Autor) FFUP; Castro, MMCA (Autor) Outra; Pedroso de Lima, MCP (Autor) Outra; Jurado, AS (Autor) Outra

Revista

Título: Biochimica et Biophysica Acta: Biomembranes

Vol. 1860

Páginas: 2619-2634

ISSN: 0005-2736

Editora: Elsevier

Indexação

ISI Web of Knowledge - 7 Citações

Scopus - 10 Citações

Outras Informações

ID Authenticus: P-00P-QNF

DOI: 10.1016/j.bbamem.2018.10.002

Abstract (EN): Background: Cell-penetrating peptides (CPPs) have been extensively exploited in gene therapy approaches as vectors for intracellular delivery of bioactive molecules. The ability of CPPs to be internalized into cells and their capacity to complex nucleic acids depend on their molecular structure, both primary and secondary, namely regarding hydrophobicity/hydrophilicity. CPP acylation has been used as a strategy to improve this structural feature. Methods: Acyl groups (from 6 to 18 carbon atoms) were attached to the S4(13)-PV peptide and their effects on the peptide competence to complex siRNAs and to mediate gene silencing in glioblastoma (GBM) cells were studied. A systematic characterization of membrane interactions with S4(13)-PV acyl-derivatives was also conducted, using different biophysical techniques (surface pressure-area isotherms in Langmuir monolayers, DSC and P-31 NMR) to unravel a relationship between CPP biological activity and CPP effects on membrane stability and lipid organization. Results: A remarkable concordance was noticed between acylated-S4(13)-PV peptide competence to promote gene silencing in GBM cells and disturbance induced in membrane models, the lauroyl- and myristoyl-S4(13)-PV peptides being the most effective. A cut-off effect was described for the first time regarding the influence of acylchain length on CPP bioactivity. Conclusions: C12-S4(13)-PV showed high capacity to destabilize lipid bilayers, to escape from lysosomal degradation and to mediate gene silencing without promoting cytotoxicity. General significance: Besides unraveling a new CPP with high potential to be employed as a gene delivery vector, this work emphasizes the benefit from allying biophysical and biological studies towards a proper CPP structural refinement for successful pre-clinical/clinical application. General significance: Besides unraveling a new CPP with high potential to be employed as a gene delivery vector, this work emphasizes the benefit from allying biophysical and biological studies towards a proper CPP structural refinement for successful pre-clinical/clinical application.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 16