Division of Molecular Physics, Department of Physics, Chemistry and Biology , Linköping University , 581 83 Linköping , Sweden.
Langmuir. 2018 Jun 5;34(22):6529-6537. doi: 10.1021/acs.langmuir.8b00592. Epub 2018 May 22.
Membrane-active peptides that enable the triggered release of liposomal cargo are of great interest for the development of liposome-based drug delivery systems but require peptide-lipid membrane interactions that are highly defined and tunable. To this end, we have explored the possibility to use the competing interactions between membrane partitioning and heterodimerization and the folding of a set of four different de novo designed coiled coil peptides. Covalent conjugation of the cationic peptides triggered rapid destabilization of membrane integrity and the release of encapsulated species. The release was inhibited when introducing complementary peptides as a result of heterodimerization and folding into coiled coils. The degree of inhibition was shown to be dictated by the coiled coil peptide heterodimer dissociation constants, and liposomal release could be reactivated by a heterodimer exchange to render the membrane bound peptide free and thus membrane-active. The possibility to tune the permeability of lipid membranes using highly specific peptide-folding-dependent interactions delineates a new possible approach for the further development of responsive liposome-based drug delivery systems.
对能够触发脂质体货物释放的膜活性肽，人们非常感兴趣，因为它们可用于开发基于脂质体的药物输送系统，但需要高度明确和可调的肽-脂质膜相互作用。为此，我们探索了使用膜分配和异二聚化以及一组四个不同从头设计的卷曲螺旋肽的折叠之间的竞争相互作用的可能性。阳离子肽的共价缀合会迅速破坏膜完整性并释放包裹的物质。当引入互补肽作为异二聚体和卷曲螺旋形成的结果时，释放会被抑制。抑制的程度取决于卷曲螺旋肽异二聚体解离常数，并且通过异二聚体交换可以重新激活脂质体释放，从而使膜结合肽自由，从而具有膜活性。使用高度特异性的肽折叠依赖性相互作用来调节脂质膜的通透性的可能性为进一步开发响应型基于脂质体的药物输送系统描绘了一种新的可能方法。
