Membrane Interactions of Novicidin, a Novel Antimicrobial Peptide: Phosphatidylglycerol Promotes Bilayer Insertion

TY - JOUR

T1 - Membrane Interactions of Novicidin, a Novel Antimicrobial Peptide: Phosphatidylglycerol Promotes Bilayer Insertion

AU - Dorosz, Jerzy

AU - Gofman, Yana

AU - Kolusheva, Sofiya

AU - Otzen, Daniel

AU - Ben-Tal, Nir

AU - Nielsen, Niels Christian

AU - Jelinek, Raz

PY - 2010

Y1 - 2010

N2 - Novicidin is an antimicrobial peptide derived from ovispirin, a cationic peptide which originated from the ovine cathelicidin SMAP-29. Novicidin, however, has been designed to minimize the cytotoxic properties of SMAP-29 and ovisipirin toward achieving potential therapeutic applications. We present an analysis of membrane interactions and lipid bilayer penetration of novicidin, using an array of biophysical techniques and biomimetic membrane assemblies, complemented by Monte Carlo (MC) simulations. The data indicate that novicidin interacts minimally with zwitterionic bilayers, accounting for its low hemolytic activity. Negatively charged phosphatidylglycerol, on the other hand, plays a significant role in initiating membrane binding of novicidin, and promotes peptide insertion into the interface between the lipid headgroups and the acyl chains. The significant insertion into bilayers containing negative phospholipids might explain the enhanced antibacterial properties of novicidin. Overall, this study highlights two distinct outcomes for membrane interactions of novicidin, and points to a combination between electrostatic attraction to the lipid/water interface and penetration into the subsurface lipid headgroups region as important determinants for the biological activity of novicidin.

AB - Novicidin is an antimicrobial peptide derived from ovispirin, a cationic peptide which originated from the ovine cathelicidin SMAP-29. Novicidin, however, has been designed to minimize the cytotoxic properties of SMAP-29 and ovisipirin toward achieving potential therapeutic applications. We present an analysis of membrane interactions and lipid bilayer penetration of novicidin, using an array of biophysical techniques and biomimetic membrane assemblies, complemented by Monte Carlo (MC) simulations. The data indicate that novicidin interacts minimally with zwitterionic bilayers, accounting for its low hemolytic activity. Negatively charged phosphatidylglycerol, on the other hand, plays a significant role in initiating membrane binding of novicidin, and promotes peptide insertion into the interface between the lipid headgroups and the acyl chains. The significant insertion into bilayers containing negative phospholipids might explain the enhanced antibacterial properties of novicidin. Overall, this study highlights two distinct outcomes for membrane interactions of novicidin, and points to a combination between electrostatic attraction to the lipid/water interface and penetration into the subsurface lipid headgroups region as important determinants for the biological activity of novicidin.

KW - Amino Acid Sequence

KW - Anti-Infective Agents

KW - Antimicrobial Cationic Peptides

KW - Circular Dichroism

KW - Erythrocytes

KW - Hemolysis

KW - Humans

KW - Lipid Bilayers

KW - Microbial Sensitivity Tests

KW - Monte Carlo Method

KW - Phosphatidylglycerols

U2 - 10.1021/jp1052248

DO - 10.1021/jp1052248

M3 - Journal article

C2 - 20690652

SN - 1520-6106

VL - 114

SP - 11053

EP - 11060

JO - Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces & Biophysical

JF - Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces & Biophysical

IS - 34

ER -