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

• DOI: 10.1021/acs.jpcb.9b05512
• Publication Date: 2019-08-29T19:27:55Z
• Authors: Lucas Rodrigues d...; Ian William Hamley; Valeria Castelletto; Bianca Bonetto Mo...; Sang Won Han; Cristiano Luis Pi...; Emerson Rodrigo d...
• Keywords: DNA condensation; Cationic polymerization; Cell-penetrating peptide

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