Influence of lipid composition on membrane activity of antimicrobial phenylene ethynylene oligomers
Influence of lipid composition on membrane activity of antimicrobial phenylene ethynylene oligomers
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DOI：
10.1021/jp077487j
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发表时间：
2008-03-20
影响因子：
3.3
通讯作者：
Tew, Gregory N.
中科院分区：
文献类型：
--
作者：
Som, Abhigyan;Tew, Gregory N.
宿主防御肽（宿主防御肽）是先天免疫系统的一部分，选择性地靶向细菌细胞膜而不是宿主细胞膜。因此，它们的抗菌性能一直受到密切的研究。它们的选择性很大程度上取决于构成不同细胞膜的脂质的化学性质和主要的结构性质。合成HDP模拟物的能力最近得到了证实。为了更好地了解这些HDP模拟物是如何与双层膜相互作用的，研究了三种具有间苯基乙烯基主链和烷基胺侧链的同源抗菌低聚物（AMOs） 1-3。其中，AMO 1无活性，AMO 2具有特异性活性，AMO 3对人类红细胞（哺乳动物细胞的标准模型）上的细菌具有非特异性活性。这三种AMOs与具有不同脂质组成的脂质体的相互作用使用荧光染料泄漏试验进行了详细表征。由PE/PG脂质组成的细菌膜模拟脂质体中，AMO 2和AMO 3比AMO 1渗漏更多。大肠杆菌脂质囊泡的使用也得到了相同的结果。脂质组成的进一步变化表明，与哺乳动物细胞膜的主要成分PC、PC/PG或PC/PS脂质相比，AMO 2对PE/PG和大肠杆菌脂质具有更高的选择性亲和力。相比之下，AMO 3缺乏这种脂质选择性，与所有脂质体相互作用同样容易；AMO 1保持失活状态。这些观察结果表明，脂质类型和结构在决定膜选择性方面比脂质头基团电荷更重要。
Host defense peptides (HDPs), part of the innate immune system, selectively target the membranes of bacterial cells over that of host cells. As a result, their antimicrobial properties have been under intense study. Their selectivity strongly depends on the chemical and mostly structural properties of the lipids that make up different cell membranes. The ability to synthesize HDP mimics has recently been demonstrated. To better understand how these HDP mimics interact with bilayer membranes, three homologous antimicrobial oligomers (AMOs) 1-3 with an m-phenylene ethynylene backbone and alkyl amine side chains were studied. Among them, AMO 1 is nonactive, AMO 2 is specifically active, and AMO 3 is nonspecifically active against bacteria over human red blood cells, a standard model for mammalian cells. The interactions of these three AMOs with liposomes having different lipid compositions are characterized in detail using a fluorescent dye leakage assay. AMO 2 and AMO 3 caused more leakage than AMO 1 from bacteria membrane mimic liposomes composed of PE/PG lipids. The use of E. coli lipid vesicles gave the same results. Further changes of the lipid compositions revealed that AMO 2 has selectively higher affinity toward PE/PG and E. coli lipids than PC, PC/PG or PC/PS lipids, the major components of mammalian cell membranes. In contrast, AMO 3 is devoid of this lipid selectivity and interacts with all liposomes with equal ease; AMO 1 remains inactive. These observations suggest that lipid type and structure are more important in determining membrane selectivity than lipid headgroup charges for this series of HDP mimics.