1.D.32 The Pore-forming Novicidin (Novicidin) Family

Novicidin is an 18-residue cationic 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.

Dorosz et al. 2010 presented 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. Insertion into bilayers containing negative phospholipids might explain the enhanced antibacterial properties of novicidin. A combination of electrostatic attraction to the lipid/water interface and penetration into the subsurface lipid headgroup region are determinants of activity. 

Novicidin forms toroidal pores at high concentrations leading to fairly extensive membrane lipid disturbance (Bertelsen et al. 2012).  Peptide binding may first induce leakage at a critical surface concentration, probably through formation of transient pores or transient disruption of the membrane integrity, followed by more extensive membrane disintegration at higher P/L ratios (Nielsen and Otzen 2010).

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