Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
Chem Commun (Camb). 2020 Dec 21;56(100):15655-15658. doi: 10.1039/d0cc06312f. Epub 2020 Dec 8.
The effects of all-hydrocarbon cross-linking on the cell-penetrating properties of Tat were systematically investigated. These stapled cell-penetrating peptides were designed to exhibit a cationic secondary amphipathic profile. We found that the hydrophobicity and helical conformation of these hydrocarbon staple peptides correlate well with their cellular uptake efficiency. Our results also revealed that higher affinity to heparan sulfate of the rigid stapled Tat peptides correlated well with the higher cellular uptake compared with non-stapled Tat peptides with flexible charge display. Notably, the stapled Tat peptides showed increased endosomal escape, high proteolytic stability, and low cytotoxicity. Therefore, they present a potent system for the intracellular transport of bioactive cargos.
系统研究了全碳氢化合物交联对 Tat 细胞穿透特性的影响。这些订书钉状的细胞穿透肽被设计成表现出阳离子性的二级两亲性结构。我们发现，这些碳氢化合物订书钉肽的疏水性和螺旋构象与其细胞摄取效率密切相关。我们的结果还表明，刚性订书钉状 Tat 肽与肝素硫酸更高的亲和力与与具有柔性电荷显示的非订书钉状 Tat 肽相比，具有更高的细胞摄取率密切相关。值得注意的是，订书钉状 Tat 肽表现出增强的内体逃逸、高蛋白水解稳定性和低细胞毒性。因此，它们为生物活性有效载荷的细胞内运输提供了一个有效的系统。
