Lipid Clustering by Three Homologous Arginine-Rich Antimicrobial Peptides is Insensitive to Amino Acid Arrangement Academic Article uri icon

abstract

  • Membrane and antimicrobial properties of three short Arg-rich peptides containing the same amino acid composition but different sequences were determined in this study. These peptides, PFWRIRIRR-amide (PR-9), RRPFWIIRR-amide (RR-9) and PRFRWRIRI-amide (PI-9), all exhibit the ability to induce segregation of the anionic lipids from the zwitterionic lipids, as shown by changes in the phase transition properties of lipid mixtures detected by differential scanning calorimetry and also by freeze fracture electron microscopy. The Minimal Inhibitory Concentration (MIC) of these three peptides against several strains of Gram positive bacteria correlated well with the lipid composition of the bacterial membrane. The lower activity of these three peptides against Gram negative bacteria, particularly PI-9, could be explained by the interactions of these peptides with LPS as shown by isothermal titration calorimetry. The promotion of lipid domains by PR-9 as well as by a cathelicidin fragment, KR-12 that had previously been shown to induce lipid phase segregation, was directly visualized using freeze fracture electron microscopy. This work shows the insensitivity of phase segregation to the specific arrangement of the cationic charges in the sequence of these small cationic peptides as well as being independent of their tendency to form different secondary structures.

publication date

  • January 1, 2010