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On the interaction of the highly charged peptides casocidins with biomimetic membranes
Bioelectrochemistry ( IF 5 ) Pub Date : 2018-04-19 , DOI: 10.1016/j.bioelechem.2018.04.012
Lucia Becucci , Giovanni Aloisi , Andrea Scaloni , Simonetta Caira , Rolando Guidelli

Casocidin I and II (CI and CII) are structurally related antimicrobial peptides made of 39 and 31 amino acids, respectively, which derive from natural proteolytic processing of αs2-casein and adopt an ordered α-helical structure in biomimetic membranes. Their putative membrane-permeabilizing activity was investigated at Hg-supported self-assembled monolayers (SAMs) and at tethered bilayer lipid membranes (tBLMs); the latter consisted of a monolayer of 2,3,di-O-phytanyl-sn-glycerol-1-tetraethylene-glycol-d,l-α lipoic acid ester thiolipid (DPTL), with a dioleoylphosphatidylcholine (DOPC) or dioleoylphosphatidylserine (DOPS) monolayer on top of it. Interaction of CI and CII with these biomimetic membranes was studied by four electrochemical techniques at pH 3, 5.4 and 6.8. Peptide incorporation in tBLMs was attempted via scans of electrochemical impedance spectra. Experiments demonstrated that CI and CII penetrate SAMs as well as the distal DOPC monolayer of DPTL/DOPC tBLMs, but not the proximal phytanyl monolayer, with the only exception of CII at pH 5.4. Conversely, CII permeabilized DPTL/DOPS tBLMs to a moderate extent at all investigated pH values by forming holes across the membrane, but not ion channels. Structural distribution of charged residues seemed to prevent CII from having a hydrophobic side of the α-helix capable of stabilizing a regular ion channel in the lipid matrix.



中文翻译:

关于高电荷肽casocidins与仿生膜的相互作用

Casocidin I和II(CI和CII)在结构上与分别制成的39个31个氨基酸,抗微生物肽,其由α的天然蛋白水解加工派生S2 -酪蛋白和在仿生膜采用有序α螺旋结构。在汞支持的自组装单层膜(SAMs)和拴系双层脂质膜(tBLMs)上研究了其推定的膜通透活性。后者包括了2,3,二-单层的ö -phytanyl- SN -甘油-1-四-乙二醇d-α硫辛酸酯硫醇脂(DPTL),在其顶部具有单油酰磷脂酰胆碱(DOPC)或单油酰磷脂酰丝氨酸(DOPS)单层。通过四种电化学技术在pH 3、5.4和6.8下研究了CI和CII与这些仿生膜的相互作用。通过扫描电化学阻抗谱来尝试将肽掺入tBLM。实验表明,CI和CII可以穿透SAM以及DPTL / DOPC tBLM的远端DOPC单层,但不能穿透近植烷酰基单层,只有CII在pH 5.4时例外。相反,CII通过在整个膜上形成孔而不是在离子通道上形成孔,从而在所有研究的pH值下均能适度地渗透DPTL / DOPS tBLM。

更新日期:2018-04-19
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