Inter-polyelectrolyte nano-assembly induces folding and activation of functional peptides
Inter-polyelectrolyte nano-assembly induces folding and activation of functional peptides
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聚电解质间纳米组装诱导功能肽的折叠和激活
DOI：
10.1016/j.jconrel.2015.10.001
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
A. Maruyama
中科院分区：
文献类型：
--
作者：
N. Shimada;H. Kinoshita;S;Tokunaga;T. Umegae;N. Kume;W. Sakamoto;A. Maruyama
溶解性不足、脆弱的折叠结构和较短的半衰期往往阻碍了多肽作为生物试剂或治疗方法的使用。为了增强多肽的功能，本研究测试了这些多肽与具有水溶性接枝链的离子接枝共聚物的络合效果。两亲性阴离子多肽E5由于从无规卷曲状态折叠到有序的α-螺旋结构，在酸性pH下获得了膜破坏活性。多肽的聚集和不精确折叠限制了多肽的膜破坏活性。在阳离子接枝共聚物存在下，E5及其类似物呈有序构象，没有聚集。多肽和共聚物的混合物不仅在酸性pH下，而且在中性pH下都比多肽单独作用更有效，在中性pH下，多肽单独没有活性。类似地，阳离子多肽被阴离子接枝共聚物成功折叠并活化。因此，我们的分析表明，离子多肽与具有相反离子电荷的接枝共聚物的自发纳米组装可以触发多肽的折叠，而不会损失溶解性，从而导致生物活性增强。
Insufficient solubility, fragile folding structure and short half-life frequently hamper use of peptides as biological reagents or therapies. To enhance the peptide function, the effect of complexation of the peptides with ionic graft copolymers with water-soluble graft chains was tested in this study. Amphiphilic anionic peptide E5 acquires membrane disrupting activity at acidic pH due to folding from the random coil state to an ordered α-helical structure. Aggregation and imprecise folding of the peptide limited membrane disrupting activity of the peptide. In the presence of a cationic graft copolymer, E5 and its analogs adopted an ordered conformation without aggregation. The mixture of the peptides and the copolymer functioned more efficiently than peptide alone at not only acidic pH but also neutral pH at which the peptide alone had no activity. Similarly, a cationic peptide was successfully folded and activated by an anionic graft copolymer. Thus, our analysis indicated that spontaneous nano-assembly of ionic peptides with graft copolymers having opposite ionic charges triggers the folding of peptides without loss of solubility, leading to enhanced bioactivity.