Structural studies and model membrane interactions of two peptides derived from bovine lactoferricin
Structural studies and model membrane interactions of two peptides derived from bovine lactoferricin
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DOI：
10.1002/psc.629
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发表时间：
2005-07-01
影响因子：
2.1
通讯作者：
Vogel, HJ
中科院分区：
文献类型：
--
作者：
Nguyen, LT;Schibli, DJ;Vogel, HJ
牛乳铁蛋白B（LfcinB）具有很强的抗菌活性，是一种新型抗菌剂。据报道，LfcinB的11个残基的线性肽部分具有与乳铁蛋白本身相似的抗微生物活性，但具有较低的溶血活性。该肽的膜结合和膜扰动特性与具有添加的二硫键的酰胺化合成版本一起进行了研究，其设计用于赋予增加的稳定性和可能的活性。通过溶血试验测量了这些肽对金黄色葡萄球菌和大肠杆菌的抗微生物和细胞毒性。还在针对神经母细胞瘤细胞系的抗癌测定中测试肽。使用荧光报告分子钙黄绿素研究了由这些LfcinB衍生物引起的囊泡破坏。通过荧光定量两个Trp残基在模拟膜环境中的埋藏程度。最后，结合到SDS胶束的肽的溶液NMR结构被确定，以提供深入了解它们的膜结合状态。发现环状肽比其线性对应物具有更大的抗微生物效力。与此性质一致，修饰肽的两个Trp残基被认为嵌入膜更深处。尽管两种肽均采用两亲性结构而没有任何规则的α-螺旋或β-折叠构象，但3D结构揭示了环状肽的阳离子和疏水表面的更清晰的划分。版权所有（c）2004欧洲肽协会和约翰威利父子有限公司。
The powerful antimicrobial properties of bovine lactoferricin (LfcinB) make it attractive for the development of new antimicrobial agents. An 11-residue linear peptide portion of LfcinB has been reported to have similar antimicrobial activity to lactoferricin itself, but with lower hemolytic activity. The membrane-binding and membrane-perturbing properties of this peptide were studied together with an amidated synthetic version with an added disulfide bond, which was designed to confer increased stability and possibly activity. The antimicrobial and cytotoxic properties of the peptides were measured against Staphylococcus aureus and Escherichia coli and by hemolysis assays. The peptides were also tested in an anti-cancer assay against neuroblastoma cell lines. Vesicle disruption caused by these LfcinB derivatives was studied using the fluorescent reporter molecule calcein. The extent of burial of the two Trp residues in membrane mimetic environments were quantitated by fluorescence. Finally, the solution NMR structures of the peptides bound to SDS micelles were determined to provide insight into their membrane bound state. The cyclic peptide was found to have greater antimicrobial potency than its linear counterpart. Consistent with this property, the two Trp residues of the modified peptide were suggested to be embedded deeper into the membrane. Although both peptides adopt an amphipathic structure without any regular a-helical or beta-sheet conformation, the 3D-structures revealed a clearer partitioning of the cationic and hydrophobic faces for the cyclic peptide. Copyright (c) 2004 European Peptide Society and John Wiley & Sons, Ltd.