PDF(Pubmed)
Abstract：
Cell-penetrating peptides (CPPs) are widely used for the intracellular delivery of a variety of cargo molecules, including small molecules, peptides, nucleic acids, and proteins. Many cationic and amphiphilic CPPs have been developed; however, there have been few reports regarding hydrophobic CPPs. Herein, we have developed stapled hydrophobic CPPs based on the hydrophobic CPP, TP10, by introducing an aliphatic carbon side chain on the hydrophobic face of TP10. This side chain maintained the hydrophobicity of TP10 and enhanced the helicity and cell penetrating efficiency. We evaluated the preferred secondary structures, and the ability to deliver 5(6)-carboxyfluorescein (CF) as a model small molecule and plasmid DNA (pDNA) as a model nucleotide. The stapled peptide F-3 with CF, in which the stapling structure was introduced at Gly residues, formed a stable α-helical structure and the highest cell-membrane permeability via an endocytosis process. Meanwhile, peptide F-4 demonstrated remarkable stability when forming a complex with pDNA, making it the optimal choice for the efficient intracellular delivery of pDNA. The results showed that stapled hydrophobic CPPs were able to deliver small molecules and pDNA into cells, and that different stapling positions in hydrophobic CPPs can control the efficiency of the cargo delivery.
摘要：
细胞穿透肽(CPPs)广泛用于细胞内递送多种货物分子,包括小分子，肽，核酸,和蛋白质。已经开发了许多阳离子和两亲性CPP；然而，关于疏水性CPPs的报道很少。在这里，我们在疏水性CPP的基础上开发了装订的疏水性CPP，TP10，通过在TP10的疏水性面上引入脂肪碳侧链。该侧链保持了TP10的疏水性并增强了螺旋性和细胞穿透效率。我们评估了首选的二级结构，以及递送作为模型小分子的5(6)-羧基荧光素(CF)和作为模型核苷酸的质粒DNA(pDNA)的能力。带有CF的钉合肽F-3，在Gly残基处引入钉合结构，通过内吞过程形成稳定的α-螺旋结构和最高的细胞膜通透性。同时,当与pDNA形成复合物时，肽F-4表现出显著的稳定性，使其成为有效细胞内传递pDNA的最佳选择。结果表明，钉合的疏水CPPs能够将小分子和pDNA递送到细胞中，并且疏水性CPPs中的不同钉合位置可以控制货物递送的效率。
