Cationic copolymer augments membrane permeabilizing activity of an amphiphilic peptide
Cationic copolymer augments membrane permeabilizing activity of an amphiphilic peptide
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阳离子共聚物增强两亲肽的膜透化活性
DOI：
10.1080/09205063.2017.1293483
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
A. Maruyama
中科院分区：
文献类型：
--
作者：
W. Sakamoto;T. Ochiai;N. Shimada;A. Maruyama
膜破坏肽（也称为膜融合肽）已用于大分子如核酸和蛋白质的胞质递送。我们以前报道，阳离子接枝共聚物，聚（烯丙胺）-接枝葡聚糖（PAA-g-Dex），增强膜破坏活性的带负电荷的E5肽。在酸性和中性pH下，该共聚物的存在下观察到了较强的膜破坏活性。本文进一步探讨了E5/PAA-g-Dex混合物的活性。E5/PAA-g-Dex的膜透化活性依赖于E5和PAA-g-Dex的浓度，表明E5和PAA-g-Dex之间的复合物产生活性。由于肽/PAA-g-Dex的活性是肽序列特异性的，我们推断PAA-g-Dex通过促进E5折叠成其活性构象来激活膜透化活性。E5/PAA-g-Dex的膜透化活性导致牛血清白蛋白转运到HL-60细胞中，细胞毒性低于毛地黄皂苷，毛地黄皂苷是一种天然存在的表面活性剂，用于将大分子递送到细胞中。
Membrane disruptive peptides (also called membrane fusogenic peptides) have been employed for cytosolic delivery of macromolecules such as nucleic acids and proteins. We reported previously that the cationic graft copolymer, poly(allylamine)-graft-dextran (PAA-g-Dex), augments membrane disruptive activity of the negatively charged E5 peptide. Strong membrane disruptive activity was observed in the presence of the copolymer at both acidic and neutral pH. In this paper, activities of E5/PAA-g-Dex mixture were further explored. Membrane permeabilization activity of E5/PAA-g-Dex was dependent on concentrations of both E5 and PAA-g-Dex, indicating that a complex between E5 and PAA-g-Dex produced the activity. Since the activity of peptide/PAA-g-Dex was peptide sequence-specific, we reasoned that PAA-g-Dex activated membrane-permeabilization activity by facilitating folding of E5 into its active conformation. The membrane permeabilization activity of E5/PAA-g-Dex resulted in transportation of bovine serum albumin into HL-60 cells with less cellular toxicity than digitonin, a naturally occurring surfactant used for delivery of macromolecules into cells.