Interactions of the Australian tree frog antimicrobial peptides aurein 1.2, citropin 1.1 and maculatin 1.1 with lipid model membranes: Differential scanning calorimetric and Fourier transform infrared spectroscopic studies |
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Authors: | Gordon WJ Seto Daniel M Kobewka Frances Separovic |
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Institution: | a Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7 b School of Chemistry, Bio21 Institute, University of Melbourne, Melbourne VIC 3010, Australia |
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Abstract: | The interactions of the antimicrobial peptides aurein 1.2, citropin 1.1 and maculatin 1.1 with dimyristoylphosphatidylcholine (DMPC), dimyristoylphosphatidylglycerol (DMPG) and dimyristoylphosphatidylethanolamine (DMPE) were studied by differential scanning calorimetry (DSC) and Fourier-transform infrared (FTIR) spectroscopy. The effects of these peptides on the thermotropic phase behavior of DMPC and DMPG are qualitatively similar and manifested by the suppression of the pretransition, and by peptide concentration-dependent decreases in the temperature, cooperativity and enthalpy of the gel/liquid-crystalline phase transition. However, at all peptide concentrations, anionic DMPG bilayers are more strongly perturbed than zwitterionic DMPC bilayers, consistent with membrane surface charge being an important aspect of the interactions of these peptides with phospholipids. However, at all peptide concentrations, the perturbation of the thermotropic phase behavior of zwitterionic DMPE bilayers is weak and discernable only when samples are exposed to high temperatures. FTIR spectroscopy indicates that these peptides are unstructured in aqueous solution and that they fold into α-helices when incorporated into lipid membranes. All three peptides undergo rapid and extensive H-D exchange when incorporated into D2O-hydrated phospholipid bilayers, suggesting that they are located in solvent-accessible environments, most probably in the polar/apolar interfacial regions of phospholipid bilayers. The perturbation of model lipid membranes by these peptides decreases in magnitude in the order maculatin 1.1 > aurein 1.2 > citropin 1.1, whereas the capacity to inhibit Acholeplasma laidlawii B growth decreases in the order maculatin 1.1 > aurein 1.2 ≅ citropin 1.1. The higher efficacy of maculatin 1.1 in disrupting model and biological membranes can be rationalized by its larger size and higher net charge. However, despite its smaller size and lower net charge, aurein 1.2 is more disruptive of model lipid membranes than citropin 1.1 and exhibits comparable antimicrobial activity, probably because aurein 1.2 has a higher propensity for partitioning into phospholipid membranes. |
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Keywords: | AMP antimicrobial peptide DSC differential scanning calorimetry FTIR Fourier-transform infrared PC phosphatidylcholine PE phosphatidylethanolamine PG phosphatidylglycerol NMR nuclear magnetic resonance POPC 1-palmitoyl 2-oleoyl phosphatidylcholine POPG 1-palmitoyl 2-oleoyl phosphatidylglycerol DMPC dimyristoylphosphatidylcholine DMPG dimyristoylphosphatidylglycerol DMPE dimyristoylphosphatidylethanolamine DOPE dioleoylphosphatidylethanolamine DOPG dioleoylphosphatidylglycerol HPLC high performance liquid chromatography MLV multilamellar vesicles LD50 concentration required for 50% growth inhibition MIC minimum inhibitory concentration |
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