Peptide interactions, phospholipid antimicrobial peptides

Papo N, Shai Y (2003) Can we predict biological activity of antimicrobial peptides from their interactions with model phospholipid membranes Peptides 24 1693-1703... 

Other peptides containing histidines listed in Table 16.2, such as those of the histatin family (antimicrobial peptides), Sea Urchin (B18) and LAH4, strongly interact with phospholipid membranes and destabilize them. LAH4, which does not contain other cationic residues, exhibits a-helix and is more active in an acidic medium. These peptides could be putative endosome disrupting helpers that have not yet been used for polyfection. 

The interactions of several peptides with phospholipids have been studied by computer simulation. Emphasis has been given to several aspects of protein-phospholipid interactions, including the way of association and orientational preference of peptides in contact with a bilayer, the effect of phospholipids on the preference and stability of helical conformations, and the effect of the inserted peptide on the structure and dynamics of the phospholipids. These investigations have been extended to bundles of helices and even whole pore-forming proteins. In particular, the simulation of ion channels and of peptides with antimicrobial action has attracted a great deal of attention in theoretical studies. 

Prenner EJ, Lewis RNAH, McElhaney RN. The interaction of the antimicrobial peptide gramicidin S with lipid bilayer model and biological membranes. Biochim. Biophys. Acta 1999 1462 201-221. Papahadjonponlos D, Moscarello M, Eylar EH, Isaac T. Effects of proteins on thermotropic phase transitions of phospholipid membranes. Biochim. Biophys. Acta 1975 401 317-335. 

Much data have now shown that peptides, proteins, and lipids exhibit antimicrobial activity. The selective toxicity of peptides toward bacterial cells is primarily due to an initial electrostatic interaction between the peptide and the anionic phospholipid headgroups in the outer leaflet of the bacterial cytoplasmic membrane (Zasloff, 1987 Yeaman and Yount, 2003). A diversity of antimicrobial peptide sequences and structures have been discovered (Yeaman and Yount, 2003 Lai and GaUo, 2009), and this diversity underscores the reality that no single antimicrobial peptide sequence has emerged as an effective antimicrobial. Furthermore, the diversity of molecules as antimicrobials may be an evolutionary strategy to prevent or delay the development of microbial resistance to antimicrobial peptides. 

Hansen et al. showed from molecular dynamics experiments P NMR solid state spectra are simulated. This was used to investigate the interaction between of lipid bilayers containing the antimicrobial peptides e.g. alamethicin. Close agreement was found for a range of peptides between simulation and experimental results. A comment was made on the diffusion rate of the phospholipids and the effect it has the NMR spectra. ... 

Ningsih, Z. Hossain, M. A. Wade, J. D. Clayton, A. H. A. Gee, M. L. Slow insertion kinetics during interaction of a model antimicrobial peptide with unilamellar phospholipid vesicles. Langmuir 2012, 28, 2217-2224. 

Agawa Y, Lee S, Ono S, Aoyagi H, Ohno M, Tamguchi T, Anzai K, Kirino Y. Interaction with phospholipid bilayets. ion channel formation, aird antimicrobial activity of basic amphiphilic alpha-helical model peptides of various chain lengths. J Biol Chem 1991 266 20218-20222. 

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