Structure/Function Analysis of Peptoid/Lipitoid:DNA Complexes

Abstract

Previous transfection studies of cationic peptoid polymers (N-substituted polyglycines) and cationic lipitoid polymers (peptoid-phospholipid conjugates) have shown that only the polymers which possessed a repeating (cationic, hydrophobic, hydrophobic) substituent sequence are efficient in gene transfer in vitro. To determine if there is a physical attribute of peptoid and lipitoid complexes that correlates with efficient gene transfection, biophysical, and transfection measurements were performed with polymer:DNA complexes containing each of seven structurally diverse peptoid polymers and two lipitoids that possess different hydrophobic substituents. These measurements revealed that the biophysical properties of these complexes (size, zeta-potential, ethidium bromide exclusion) varied with polymer structure and complex (+/-) charge ratio but were not directly predictive of transfection efficiency. Unique alterations in the circular dichroism spectra of DNA were observed in complexes containing several of the peptoids and both lipitoids, although FTIR spectroscopy demonstrated that the DNA remained in the B-form. The lack of correlations between the physical properties and the transfection activities of these polyplexes suggests that a further subpopulation examination of these complexes by these methods may reveal hidden structure-activity relationships.

Bio-nano complexes: DNA/surfactant/single-walled carbon nanotube interactions in electric field

“…The native 'B-form' DNA helix has a unique circular dichroism (CD) spectrum that consists of positive and negative bands near 275 nm and 245 nm, respectively [34,70,71]. The shift of those bands and the change in their spectral shape indicate the rearrangement of the helical structure of DNA.…”

New trends in peptide-based anti-biofilm strategies: a review of recent achievements and bioinformatic approaches

“…DNA binding may facilitate the detachment or disruption of biofilm structures, since it has been reported that eDNA is involved in cell-cell attachment, having an important role in cell adhesion to surfaces and cell aggregation (AllesenHolm et al 2006;Das et al 2010). This is the case for cationic AMPs and peptoids (Lobo et al 2003;Otvos 2005;Hale and Hancock 2007). For example, the development of P. aeruginosa biofilms is disrupted by the enzyme DNase I (Whitchurch et al 2002).…”

Antimicrobial Peptoids Are Effective against Pseudomonas aeruginosa Biofilms

“…Bacterial detachment from the surface by peptoids resulted in biomass reduction. Cationic AMPs and peptoids are known to bind DNA (10,16,21), and this binding may facilitate detachment or disruption of otherwise-stable biofilm structures. It has previously been reported that extracellular DNA (eDNA) is involved in cell-cell attachment (1); the development of P. aeruginosa biofilms is disrupted by DNase I (31).…”