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Nanoscopic Structure of Complexes Formed between DNA and the Cell-Penetrating Peptide Penetratin

Texto completo
de Mello, Lucas Rodrigues [1] ; Hamley, Ian William [2] ; Castelletto, Valeria [2] ; Moreno Garci, Bianca Bonetto [1] ; Han, Sang Won [1] ; Pinto de Oliveira, Cristiano Luis [3] ; da Silv, Emerson Rodrigo a [1]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Fed Sao Paulo, Dept Biofis, BR-04023062 Sao Paulo - Brazil
[2] Univ Reading, Dept Chem, Reading RGD 6AD, Berks - England
[3] Univ Sao Paulo, Inst Fis, BR-05508090 Sao Paulo - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: Journal of Physical Chemistry B; v. 123, n. 42, p. 8861-8871, OCT 24 2019.
Citações Web of Science: 0

One of the most remarkable examples of cell-penetrating peptides (CPPs) is Penetratin, a 16-mer fragment derived from the Drosophila Antennapedia homeobox. Understanding the structure of Penetratin/DNA complexes is a key factor for the successful design of new vectors for gene delivery and may assist in optimizing molecular carriers based on CPPs. Herein, we present a comprehensive study on the nanoscale structure of noncovalent complexes formed between Penetratin and DNA. The strong cationic nature of the peptide makes it a very efficient agent for condensing DNA strands via electrostatic attraction, and we show for the first time that DNA condensation is accompanied by random-to-beta-sheet transitions of Penetratin secondary structure, demonstrating that nucleic acids behave as a structuring agent upon complexation. For the first time, nanoscale-resolved spectroscopy is used to provide single-particle infrared data from DNA carriers based on CPPs, and they show that the structures are stabilized by Penetratin beta-sheet cores, whereas larger DNA fractions are preferentially located in the periphery of aggregates. In-solution infrared assays indicate that phosphate diester groups are strongly affected upon DNA condensation, presumably as a consequence of charge delocalization induced by the proximity of cationic amide groups in Penetratin. The morphology is characterized by nanoassemblies with surface fractal features, and short-range order is found in the inner structure of the scaffolds. Interestingly, the formation of beads-on-a-string arrays is found, producing nanoscale architectures that resemble structures observed in early steps of chromatin condensation. A complexation pathway where DNA condensation and peptide pairing into beta-sheets are key steps for organization is proposed. (AU)

Processo FAPESP: 15/20206-8 - Modulação de monócitos, macrófagos e pericitos pelos genes dos fatores estimuladores de colônia para tratamento de isquemia de membros em modelo murino
Beneficiário:Sang Won Han
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