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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Self-assembly and intracellular delivery of DNA by a truncated fragment derived from the Trojan peptide Penetratin

Texto completo
Autor(es):
Mello, Lucas R. [1] ; Hamley, Ian W. [2] ; Castelletto, Valeria [2] ; Garcia, Bianca B. M. [1] ; Lourenco, Thiago C. [1] ; Vassiliades, Sandra V. [3] ; Alves, Wendel A. [3] ; Han, Sang W. [1] ; Silva, Emerson R. [1]
Número total de Autores: 9
Afiliação do(s) autor(es):
[1] Univ Fed Sao Paulo, Dept Biofis, BR-04023062 Sao Paulo, SP - Brazil
[2] Univ Reading, Dept Chem, Reading RGD 6AD, Berks - England
[3] Univ Fed ABC, Ctr Ciencias Nat & Humans, BR-09210580 Santo Andre, SP - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: SOFT MATTER; v. 16, n. 20, p. 4746-4755, MAY 28 2020.
Citações Web of Science: 0
Resumo

Penetratin is a short Trojan peptide that attracts great interest in biomedical research for its capacity to translocate biological membranes. Herein, we study in detail both self-assembly and intracellular delivery of DNA by the heptamer KIWFQNR, a truncated peptide derived from Penetratin. This shortened sequence possesses a unique design with bolaamphiphilic characteristics that preserves the longest noncationic amino acid portion found in Penetratin. These features convey amphipathicity to assist self-assembly and make it a suitable model for exploring the role of hydrophobic residues for peptide interaction and cell uptake. We show that the fragment forms peptiplexes (i.e., peptide-DNA complexes), and aggregates into long nanofibers with clear beta-sheet signature. The supramolecular structure of nanofibers is likely composed of DNA cores surrounded by a peptide shell to which the double helix behaves as a template and induces fibrillization. A nucleation and growth mechanism proceeding through liquid-liquid phase separation of coacervates is proposed for describing the self-assembly of peptiplexes. We also demonstrate that peptiplexes deliver double-stranded 200 bp DNA into HeLa cells, indicating its potential for preparing non-viral vectors for oligonucleotides through noncovalent strategies. Since the main structural features of native Penetratin are conserved in this simpler fragment, our findings also highlight the role of uncharged amino acids for structuration, and thus for the ability of Penetratin to cross cell membranes. (AU)

Processo FAPESP: 14/50867-3 - INCT 2014: Instituto Nacional de Ciência e Tecnologia de Bioanalítica
Beneficiário:Lauro Tatsuo Kubota
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 17/02317-2 - Interfaces em materiais: propriedades eletrônicas, magnéticas, estruturais e de transporte
Beneficiário:Adalberto Fazzio
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 16/24409-3 - Peptídeos Penetrantes de Células para Transporte de DNA plasmídial e microRNA: da Estrutura Nanoscópica a Entrega de Genes.
Beneficiário:Emerson Rodrigo da Silva
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 15/24018-1 - Conjugados polímero-peptídeo para formulação de hidrogéis e seu uso em detecção
Beneficiário:Wendel Andrade Alves
Linha de fomento: Auxílio à Pesquisa - Regular