Department of Chemistry and Biochemistry, University of Berne, Freiestrasse 3, 3012 Berne, Switzerland.
Org Biomol Chem. 2013 Oct 21;11(39):6717-33. doi: 10.1039/c3ob41023d. Epub 2013 Aug 9.
Cell penetrating peptides (CPP) are peptides of 10 to 30 residues derived from natural translocating proteins. Multivalency is known to enhance cellular uptake for the Tat peptide and closely related polycationic sequences. To test whether multivalency effects on cellular uptake might also occur with other CPP types, we prepared multivalent versions of the strongly cationic Tat, the amphipathic sequences Antp, pVEC and TP10, and the polyproline helix SAP by convergent thioether ligation of the linear CPP onto multivalent scaffolds, and evaluated their uptake in HeLa and CHO cells, intracellular localization, cytotoxicity and hemolysis. While multivalency did not increase the cellular uptake of pVEC or SAP, multivalency effects on uptake comparable to Tat were observed with TP10 and Antp, which are attributable to their polycationic nature. The efficient synthetic protocol for these divalent CPP and their localization in the cytoplasm suggest that CPP might be useful for application in cargo delivery into cells.
细胞穿透肽（CPP）是源自天然转运蛋白的 10 到 30 个残基的肽。多价性已知可增强 Tat 肽和密切相关的多阳离子序列的细胞摄取。为了测试多价性是否也会影响其他 CPP 类型的细胞摄取，我们通过将线性 CPP 经硫醚键连接到多价支架上来制备强阳离子 Tat、两性序列 Antp、pVEC 和 TP10 以及多脯氨酸螺旋 SAP 的多价版本，并评估它们在 HeLa 和 CHO 细胞中的摄取、细胞内定位、细胞毒性和溶血作用。虽然多价性并没有增加 pVEC 或 SAP 的细胞摄取，但多价性对 TP10 和 Antp 的摄取作用与 Tat 相当，这归因于它们的多阳离子性质。这些二价 CPP 的高效合成方案及其在细胞质中的定位表明，CPP 可能在将货物递送到细胞中应用方面具有价值。
