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Penetration of Milk-Derived Antimicrobial Peptides into Phospholipid Monolayers as Model Biomembranes

DOI: 10.1155/2013/914540

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Abstract:

Three antimicrobial peptides derived from bovine milk proteins were examined with regard to penetration into insoluble monolayers formed with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) or 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt (DPPG). Effects on surface pressure ( ) and electric surface potential ( ) were measured, with a platinum Wilhelmy plate and with a vibrating plate. The penetration measurements were performed under stationary diffusion conditions and upon the compression of the monolayers. The two type measurements showed greatly different effects of the peptide-lipid interactions. Results of the stationary penetration show that the peptide interactions with DPPC monolayer are weak, repulsive, and nonspecific while the interactions with DPPG monolayer are significant, attractive, and specific. These results are in accord with the fact that antimicrobial peptides disrupt bacteria membranes (negative) while no significant effect on the host membranes (neutral) is observed. No such discrimination was revealed from the compression isotherms. The latter indicate that squeezing the penetrant out of the monolayer upon compression does not allow for establishing the penetration equilibrium, so the monolayer remains supersaturated with the penetrant and shows an under-equilibrium orientation within the entire compression range, practically. 1. Introduction 1.1. Structure of Antimicrobial Peptides and Their Action on Pathogenic Cell Membranes Antimicrobial peptides (AMPs), named also as antibiotic or host defense peptides (HDPs), are evolutionarily conserved components of the innate immune response of a variety of organisms, such as amphibians, invertebrates, plants, and mammals [1]. To date, ca. 2000 different AMPs have been identified or predicted [2, 3]. Many AMPs exhibit a broad spectrum of antimicrobial activity against Gram-positive and Gram-negative bacteria, fungi, parasites, enveloped viruses and cancerous cells [4–7]. In contrast to conventional antibiotics, AMPs appear to be bacteriocidal (bacteria killer) instead of bacteriostatic (bacteria growth inhibitor). They can destroy bacteria within minutes with the rate being faster than the bacteria growth rate [8]. Therefore, AMPs are recognized as potent source of pharmaceuticals for the treatments of multidrug-resistant microorganisms [1–21]. To date, several AMPs are in clinical trials [1, 5, 22]. Interest in AMPs is being constantly increasing during the last ten years which resulted in a number of publications on structure, bioactivity and mechanisms of action

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