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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 7
Affiliation:
[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
Total Affiliations: 3
Document type: Journal article
Source: Journal of Physical Chemistry B; v. 123, n. 42, p. 8861-8871, OCT 24 2019.
Web of Science Citations: 0
Abstract

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)

FAPESP's process: 15/20206-8 - Modulation of monocytes, macrophages and pericytes by the colony stimulating factor genes to treat murine limb ischemia
Grantee:Sang Won Han
Support type: Research Projects - Thematic Grants
FAPESP's process: 16/24409-3 - Cell-Penetrating Peptides for Transport of Plasmid DNA and microRNA: from Nanoscopic Structure to Gene Delivery.
Grantee:Emerson Rodrigo da Silva
Support type: Regular Research Grants