Zhu Peipei, Jin Lan
National Glycoengineering Research Center, Shandong University, Jinan, China.
Curr Protein Pept Sci. 2018;19(2):211-220. doi: 10.2174/1389203718666170710115240.
The lipid bilayer of the plasma membrane is a selective impermeable barrier for the internalization of most macromolecules. Cell penetrating peptides (CPPs) could cross the plasma membrane barrier to deliver various molecules into cells and are considered as a promising tool to deliver macromolecular drugs. However, the exact cellular uptake mechanisms of CPPs are still ambiguous. It was reported that the exact cellular uptake pathway was determined by numerous factors such as the amino acid sequences (hydrophobicity and net charge), extracellular CPP concentration, cargoes' properties, cell type and the temperature. No matter what kind of mechanisms, the electrostatic interaction between the positive charged amino acids and the membrane with negatively charged glycosaminoglycans (GAGs), especially heparan sulphate proteoglycans (HSPGs), was supposed to be the first crucial step for CPPs uptake. The first recognition triggers cytoskeletal remodeling via activating Rho/Rac GTPases and kinase C, followed by the cell surface microdomains changing, ligand binding and cellular uptake. This review briefly discusses the classification, structure-activity relationships, cellular uptake mechanisms and biomedical applications of CPPs.
质膜的脂质双层对于大多数大分子的内化来说是一个选择性的不透性屏障。细胞穿透肽（CPPs）能够穿过质膜屏障，将各种分子递送至细胞内，被认为是递送大分子药物的一种很有前景的工具。然而，CPPs确切的细胞摄取机制仍不明确。据报道，确切的细胞摄取途径由众多因素决定，如氨基酸序列（疏水性和净电荷）、细胞外CPP浓度、货物性质、细胞类型和温度。无论何种机制，带正电荷的氨基酸与带有负电荷的糖胺聚糖（GAGs），尤其是硫酸乙酰肝素蛋白聚糖（HSPGs）的膜之间的静电相互作用，被认为是CPPs摄取的第一个关键步骤。首次识别通过激活Rho/Rac GTP酶和蛋白激酶C触发细胞骨架重塑，随后是细胞表面微结构域的变化、配体结合和细胞摄取。本文综述简要讨论了CPPs的分类、构效关系、细胞摄取机制和生物医学应用。
