Conformation and interaction of the cyclic cationic antimicrobial peptides in lipid bilayers
Conformation and interaction of the cyclic cationic antimicrobial peptides in lipid bilayers
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DOI：
10.1034/j.1399-3011.2002.21003.x
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发表时间：
2002-07-01
期刊：
影响因子：
--
通讯作者：
Hodges, RS
中科院分区：
文献类型：
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作者：
Jelokhani-Niaraki, M;Prenner, EJ;Hodges, RS
为了研究肽-膜相互作用在环状阳离子肽的生物活性中的作用，使用CD和荧光光谱以及超离心技术，在中性和带负电荷的胶束和磷脂囊泡中检查了四种膜活性抗菌肽[基于短杆菌肽5（GS）]的构象和相互作用。此外，这些肽对捕获的荧光染料从磷脂酰胆碱（PC）和磷脂酰乙醇胺/磷脂酰甘油（PE/PG）的单层囊泡释放的影响进行了研究。环肽包括GS10 [Cyclo（VKL（dY）under barP）（2）]、GS12 [Cyclo（VKL（dY）under barP）（2）]、GS13 [Cyclo（VKL（dY）under barP）（2）]、GS14 [Cyclo（VKL（dY）under barP）（2）]、GS15 [Cyclo（VKL（dY）under barP）（2）]、GS15 [Cyclo（VKL（dY）under barP）（2）]、GS16 [Cyclo（VKL（dY）under barP）（2）]、GS17 [Cyclo（VKL（dY）under barP）（2）]、GS18 [Cyclo（VKL（dY）under barP）（2）]、GS19 [Cyclo（dY）under barP）（2）]、GS19 [Cyclo（dY（VKLK（dY）在bar下PKVKL（dY）在bar下P）]，GS14 [Cyclo（4）GS 14 [环状（VKL（dY），在bar下）]（加下划线的残基是C）-氨基酸），在它们的环大小、结构和两亲性方面不同，并且覆盖了广谱的溶血和抗微生物活性。肽与两性离子PC和带负电荷的PE/PG囊泡的相互作用彼此不同。疏水相互作用似乎是肽的溶血活性的主导因素，以及它们与PC囊泡的相互作用。肽的静电和疏水相互作用的组合诱导PE/PG囊泡中具有不同倾向的聚集和融合，顺序为：[D-Lys]（4）GS 14> GS 14> GS 12> GS 10。GS10和GS14明显位于膜界面的较深水平，更靠近双层的疏水核心，而GS12和[D-Lys]（4）GS14更靠近界面的外边界。由于环状阳离子肽与脂质双层的相互作用模式不同，其生物活性机制（及其与肽-脂质相互作用的关系）被证明是通用的和复杂的，并依赖于肽和膜的生物物理性质。
To investigate the role of peptide-membrane interactions in the biological activity of cyclic cationic pepticles, the conformations and interactions of four membrane-active antimicrobial pepticles [based on Gramicidin 5 (GS)] were examined in neutral and negatively charged micelles and phospholipid vesicles, using CD and fluorescence spectroscopy and ultracentrifugation techniques. Moreover, the effects of these peptides on the release of entrapped fluorescent dye from unilamellar vesicles of phosphatidycholine (PC) and phosphatidylethanolamine/phosphatidylglycerol (PE/PG) were studied. The cyclic pepticles include GS10 [Cyclo(VKL (dY) under barP)(2)], GS12 [Cyclo(VKLK (dY) under bar PKVKL (dY) under barP)], GS14 [Cyclo(VKLKV (dY) under bar PLKVKL (dY) under barP)] and [D-Lys](4)GS14 [Cyclo(VKL (dY) under barV (dY) under bar PLKVKL (dY) under barP)] (underlined residues are c)-amino acids), were different in their ring size, structure and amphipathicity, and covered a broad spectrum of 3 hemolytic and antimicrobial activities. Interaction of the pepticles with the zwitterionic PC and negatively charged PE/PG vesicles were distinct from each other. The hydrophobic interaction seems to be the dominant factor in the hemolytic activity of the peptides, as well as their interaction with the PC vesicles. A combination of electrostatic and hydrophobic interactions of the pepticles induces aggregation and fusion in PE/PG vesicles with different propensities in the order: [D-Lys](4) GS14>GS14>GS12>GS10. GS10 and GS14 are apparently located in the deeper levels of the membrane interfaces and closer to the hydrophobic core of the bilayers, whereas GS12 and [D-Lys](4) GS14 reside closer to the outer boundary of the interface. Because of differing modes of interaction of the cyclic cationic pepticles with lipid bilayers, the mechanism of their biological activity (and its relation to peptide-lipid interaction) proved to be versatile and complex, and dependent on the biophysical properties of both the peptides and membranes.