Seto Gordon W J, Marwaha Seema, Kobewka Daniel M, Lewis Ruthven N A H, Separovic Frances, McElhaney Ronald N
Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada.
Biochim Biophys Acta. 2007 Nov;1768(11):2787-800. doi: 10.1016/j.bbamem.2007.07.018. Epub 2007 Aug 10.
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 alpha-helices when incorporated into lipid membranes. All three peptides undergo rapid and extensive H-D exchange when incorporated into D(2)O-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 congruent with 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.
通过差示扫描量热法（DSC）和傅里叶变换红外（FTIR）光谱研究了抗菌肽奥瑞因1.2、柑橘素1.1和黄斑蛙肽1.1与二肉豆蔻酰磷脂酰胆碱（DMPC）、二肉豆蔻酰磷脂酰甘油（DMPG）和二肉豆蔻酰磷脂酰乙醇胺（DMPE）的相互作用。这些肽对DMPC和DMPG热致相行为的影响在性质上相似，表现为对预转变的抑制，以及肽浓度依赖性地降低凝胶/液晶相转变的温度、协同性和焓。然而，在所有肽浓度下，阴离子DMPG双层比两性离子DMPC双层受到的扰动更强，这与膜表面电荷是这些肽与磷脂相互作用的一个重要方面一致。然而，在所有肽浓度下，两性离子DMPE双层热致相行为的扰动较弱，只有当样品暴露于高温时才能辨别。FTIR光谱表明，这些肽在水溶液中是无结构的，当掺入脂质膜时会折叠成α-螺旋。当掺入D₂O水合磷脂双层时，所有三种肽都经历快速而广泛的H-D交换，表明它们位于溶剂可及的环境中，很可能位于磷脂双层的极性/非极性界面区域。这些肽对模型脂质膜的扰动程度按黄斑蛙肽1.1>奥瑞因1.2>柑橘素1.1的顺序降低，而抑制莱氏无胆甾原体B生长的能力按黄斑蛙肽1.1>奥瑞因1.2≈柑橘素1.1的顺序降低。黄斑蛙肽1.1在破坏模型膜和生物膜方面具有更高的效力，这可以通过其更大的尺寸和更高的净电荷来解释。然而，尽管奥瑞因1.2尺寸较小且净电荷较低，但它比柑橘素1.1更能破坏模型脂质膜，并表现出相当的抗菌活性，这可能是因为奥瑞因1.2更倾向于分配到磷脂膜中。
