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 -