Accomplishment of efficient intracellular delivery of bioactive peptides and proteins have been reported via conjugation of peptides having membrane permeation ability (i.e., cell‐penetrating peptides [CPPs]), where a physiological uptake system of extracellular materials, endocytosis, often plays a role. When endocytosed, the bioactive peptides and proteins are encapsulated into vesicular compartment named endosomes, and have to escape into the cytosol with the help of tethered CPPs for obtaining the expected bioactivities. Therefore, CPPs having improved endosomolytic activity is necessary. We here introduce an approach to employ hemolytic peptides as a new class of CPPs, which was designed to attenuate their membrane perturbation ability on cell surfaces while recovering the membrane lytic activity under endosomal conditions (i.e., the attenuated cationic amphiphilic lytic [ACAL] peptides). This was realized by introducing negatively charged glutamic acid (Glu) residues into the potential hydrophobic face of the cationic amphiphilic peptides. The applicability of these peptides for CPPs was evaluated through the intracellular delivery of shepherdin, an apoptosis‐inducing peptide.

中文翻译：

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阳离子两亲溶解肽向细胞渗透肽的转化

据报道，通过结合具有膜渗透能力的肽（即细胞穿透肽[CPPs]），可以有效地在细胞内递送生物活性肽和蛋白质，其中细胞外物质的生理摄取系统（胞吞作用）经常发挥作用。当被内吞时，生物活性肽和蛋白质被封装到称为内体的囊泡隔室中，并且必须在束缚的CPP的帮助下逃逸到胞质溶胶中以获得预期的生物活性。因此，具有改善的内溶酶活性的CPP是必要的。我们在这里介绍一种将溶血肽用作新型CPP的方法，该方法旨在减弱其在细胞表面的膜扰动能力，同时在内体条件下（例如，减毒的阳离子两亲溶解[ACAL]肽）。这是通过将带负电荷的谷氨酸（Glu）残基引入阳离子两亲肽的潜在疏水面来实现的。这些肽对CPP的适用性是通过细胞内Shepherdin（一种凋亡诱导肽）的传递来评估的。