MSI-78, an analogue of the magainin antimicrobial peptides, disrupts lipid bilayer structure via positive curvature strain
MSI-78, an analogue of the magainin antimicrobial peptides, disrupts lipid bilayer structure via positive curvature strain
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DOI：
10.1016/s0006-3495(03)70031-9
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发表时间：
2003-05-01
影响因子：
3.4
通讯作者：
Ramamoorthy, A
中科院分区：
文献类型：
--
作者：
Hallock, KJ;Lee, DK;Ramamoorthy, A
在这项工作中，我们提出了抗菌肽MSI-78的细胞裂解机制的第一个表征。MSI-78是由Genaera公司设计的一种两亲性α -螺旋肽，是一种类似于magainin家族肽的合成物。采用机械排列样品的p -31核磁共振和差示扫描量热法（DSC）研究了含肽脂质双分子层。DSC结果表明，MSI-78提高了1,2-二棕榈酰磷脂酰乙醇胺的流层到倒六方的相变温度，表明该肽在脂质双层中诱导了正曲率应变。由MSI-78和1-棕榈酰-2-油酰-磷脂酰乙醇胺组成的脂质双层的P-31-NMR表明，该肽抑制了1-棕榈酰-2-油酰-磷脂酰乙醇胺的流体层状向倒六方相转变，支持DSC结果，并且即使在非常高的肽浓度（15 Mol%）下，该肽也不会诱导非层状相的形成。含有1-棕榈酰-2-油酰-磷脂酰胆碱和MSI-78的样品的P-31-NMR显示，MSI-78诱导了双层结构的显著变化，特别是在高肽浓度下。在较低浓度（1-5%）下，肽改变了双分子层的形态，其方式与环形孔的形成一致。较高浓度的肽（10-15%）导致正常六方相和层状相脂质的混合物的形成。这项工作表明，MSI-78通过正曲率应变诱导脂质双分子层的显著变化，并提出了一个与观察到的光谱变化和先前发表的工作一致的模型。
In this work, we present the first characterization of the cell lysing mechanism of MSI-78, an antimicrobial peptide. MSI-78 is an amphipathic alpha-helical peptide designed by Genaera Corporation as a synthetic analog to peptides from the magainin family. P-31-NMR of mechanically aligned samples and differential scanning calorimetry (DSC) were used to study peptide-containing lipid bilayers. DSC showed that MSI-78 increased the fluid lamellar to inverted hexagonal phase transition temperature of 1,2-dipalmitoleoyl-phosphatidylethanolamine indicating the peptide induces positive curvature strain in lipid bilayers. P-31-NMR of lipid bilayers composed of MSI-78 and 1-palmitoyl-2-oleoyl-phosphatidylethanolamine demonstrated that the peptide inhibited the fluid lamellar to inverted hexagonal phase transition of 1-palmitoyl-2-oleoyl-phosphatidylethanolamine, supporting the DSC results, and the peptide did not induce the formation of nonlamellar phases, even at very high peptide concentrations (15 Mol%). P-31-NMR of samples containing 1-palmitoyl-2-oleoyl-phosphatidylcholine and MSI-78 revealed that MSI-78 induces significant changes in the bilayer structure, particularly at high peptide concentrations. At lower concentrations (1-5%), the peptide altered the morphology of the bilayer in a way consistent with the formation of a toroidal pore. Higher concentrations of peptide (10-15%) led to the formation of a mixture of normal hexagonal phase and lamellar phase lipids. This work shows that MSI-78 induces significant changes in lipid bilayers via positive curvature strain and presents a model consistent with both the observed spectral changes and previously published work.