Competitive double-switched self-assembled cyclic peptide nanotubes: a dual internal and external control
Competitive double-switched self-assembled cyclic peptide nanotubes: a dual internal and external control
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DOI：
10.1039/c9cp02327e
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发表时间：
2019-10-07
影响因子：
3.3
通讯作者：
Garcia-Fandino, Rebeca
中科院分区：
文献类型：
--
作者：
Calvelo, Martin;Granja, Juan R.;Garcia-Fandino, Rebeca
基于合成小分子的“智能”材料只有在特定条件下才能发挥作用，这为开发针对大量应用的受管制系统提供了新的机会。例如，对环境条件敏感的生物活性超分子实体，如细菌膜的存在，在生物医学中非常有趣。在这项工作中，我们已经设计和研究，使用分子动力学模拟，一个双重可调制的纳米管形成的环肽的自组装敏感的存在下的脂质膜和pH值的水介质。环肽被设计成在脂质双层的存在下和在低pH值下自组装成肽纳米管。在这些条件下，残留的侧链指向环肽外部，暴露于脂质双层，并且内部基团（羧酸）被质子化，从而允许水渗透并防止离子渗透。预期较高的pH值会在肽的内腔处产生羧酸根基团，导致纳米管的分解，离子被吸引并移位到双层的疏水核心，并最终杀死目标恶性细胞。我们的研究结果表明，通过在膜敏感系统中引入第二开关，可以调节其与脂质双层的相互作用。这为制备在膜水平相互作用的抗菌肽的新策略打开了大门。
"Intelligent" materials based on synthetic small molecules that become functional only under specific conditions provide new opportunities for developing regulated systems aimed at a large number of applications. For instance, biologically active supramolecular entities that are sensitive to environmental conditions, such as the presence of bacterial membranes, are extremely interesting in biomedicine. In this work, we have designed and investigated, using molecular dynamics simulations, a doubly modulable nanotube formed by the self-assembly of cyclic peptides sensitive to both the presence of a lipid membrane and the pH of the aqueous media. The cyclic peptides were designed to self-assemble into peptide nanotubes in the presence of a lipid bilayer and at low pH values. Under these conditions, the residual side chains point outside the cyclic peptides, being exposed to the lipid bilayer, and the inner groups (carboxylic acids) are protonated, thus allowing the permeation of water and preventing that of ions. Higher pH values are expected to create carboxylate groups at the lumen of the peptides, leading to the disassembly of the nanotube, the attraction and translocation of ions towards the hydrophobic core of the bilayer, and eventually killing the target malignant cells. Our results suggest that by introducing a second switch in a membrane sensitive system, it is possible to modulate its interaction with the lipid bilayer. This opens the door to new strategies for the preparation of antimicrobial peptides that interact at the membrane level.