Cationic oligopeptides modified with lipophilic fragments: Use for DNA delivery to cells

Abstract

Cationic oligopeptides, including the amphipathic α -helical peptides, are applied to the targeted delivery of DNA to eukaryotic cells due to their DNA-compacting properties and the ability to destabilize the cell lipid bilayer in some cases. We synthesized the peptides differing in the number and location of residues of decanoic acid covalently attached to Lys residues in order to combine the DNA-binding and the membrane activities in a single molecule. We chose peptide structures that assisted in the formation of α helices. The DNAbinding ability of the peptides and the membrane activity of their complexes with DNA were shown to depend on the structure. The study of erythrocyte hemolysis by complexes with DNA of the pCMV LacZ plasmid and the peculiarities of transfection of these complexes revealed a correlation between the hemolytic activity and the expression level of the lacZ gene in cells.

Characterization of iRGD-Ligand Modified Arginine-Histidine-Rich Peptides for Nucleic Acid Therapeutics Delivery to αvβ3 Integrin-Expressing Cancer Cells

“…The decrease in the efficacy of some complexes in the presence of chloroquine can be an evidence of their toxic effect on cells. A similar effect has been described previously [ 35 ]. Thus, the results obtained confirm a high specificity of RGDs carriers in targeted DNA delivery and are consistent with data from other studies [ 34 ].…”

“…The N/P ratios 8 and 12 were tried based on data from cellular uptake studies ( Figure 8 ). In order to evaluate peptide endosomolitic properties, the transfection experiments were carried out in the absence and in the presence of endosomolytic agent chloroquine which is known to destabilize membranes during the transfection process and to prevent endosomal lysis of complexes [ 35 ]. Without chloroquine, transfection efficacy in PANC-1 cells of ligand-modified DNA complexes with RGD1 and RGD2 in all the studied charge ratios and RGD3 at the 8/1 N/P ratio was 10–20-fold higher compared to unmodified RGD0/DNA polyplexes ( Figure 8 a).…”

Development of a receptor-targeted gene delivery system using CXCR4 ligand-conjugated cross-linking peptides

“…It should be noted that the spacer has a lipophilic nature and thus can provide additional protection. A positive influence of lipophilic groups in cationic peptides on their DNA‐binding and DNA‐protection properties was reported earlier in several studies .…”

Peptide-Assisted Nucleic Acid Delivery Systems on the Rise

“…Similar to GALA, JTS-1, a negatively charged amphipathic peptide with strong nonpolar amino acids in the hydrophobic domain and glutamic acid residues in the hydrophilic domain is able to form an α-helical structure [167]. Owing to the endosomolytic capacity of JTS-1-modified carriers, improved transfection activity was reported in several studies [168,169].…”