Histidine-Based Lipopeptides Enhance Cleavage of Nucleic Acids: Interactions with DNA and Hydrolytic Properties

Abstract

Interaction studies and cleavage activity experiments were carried out between plasmid DNA and a series of histidine-based lipopeptides. Specific fluorescent probes (ethidium bromide, Hoechst 33342, and pyrene) were used to monitor intercalation, minor groove binding, and self-assembly of lipopeptides, respectively. Association between DNA and lipopeptides was thus evidenced, highlighting the importance of both histidine and hydrophobic tail in the interaction process. DNA cleavage in the presence of lipopeptides was then detected by gel electrophoresis and quantified, showing the importance of histidine and the involvement of its side-chain imidazole in the hydrolysis mechanism. These systems could then be developed as synthetic nucleases while raising concern of introducing histidine in the design of lipopeptide-based transfection vectors.

A Post-segregational Killing Mechanism for Maintaining Plasmid PMF1 in Its Myxococcus fulvus Host

“…The alignment of the amino acid sequences of pMF1.20 and its homologs indicated many conserved histidine sites (Figure S4 ). Some proteins with highly conserved histidine sites are known to be nucleases, in which histidine residues are in the active center (Midon et al, 2012 ; Belieres et al, 2015 ; Sivagnanam et al, 2016 ). We speculated that pMF1.20 was probably a new kind of nuclease.…”

Amino Acid-Based Surfactants for Biomedical Applications

“…Gene transfer vectors commonly used are mostly based on viruses which arises considerable related biosafety concerns associated with carcinogenicity, immunogenicity, and broad tropism. Hence, non-viral vectors such as cationic liposomes offer a nonimmunogenic and safe method for systemic gene delivery but are, in general, less efficient than viral vectors [14,20,46,64].…”

“…DNA molecules are known to interact with single or double chain cationic surfactants, as well as with cationic gemini surfactants. Hydrophobic and electrostatic interactions occur between DNA and surfactants: the cationic group promotes the displacement of sodium cations nearby the nucleic acid, whereas hydrophobic interactions take place between the alkyl tails of surfactants; these two cooperative mechanisms promote the formation of complexes between DNA and surfactants with potential application in gene therapy [64].…”