Shen Duanwen, Liang Kexian, Ye Yunpeng, Tetteh Elizabeth, Achilefu Samuel
Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, United States.
FEBS Lett. 2007 May 1;581(9):1793-9. doi: 10.1016/j.febslet.2007.03.067. Epub 2007 Apr 4.
The nuclear internalization of biomolecules by Tat peptide provides a mechanism to deliver drugs to cells. However, translocation of molecular imaging probes to the nucleus may induce undesirable mutagenesis. To assess the feasibility of retaining its cell permeating effect without nuclear translocation, Tat-peptide was conjugated with a somatostatin receptor (STR)-avid ligand (Oct) and labeled with fluorescent dyes. The results show that Tat-Oct-5-FAM (fluorescein 5'-carboxylic acid) remained in the cytoplasm of STR-positive AR42J cells. Co-incubation of Tat-Oct-5-FAM with ATP induced nuclear translocation. These data suggest that both dye and Oct-STR endocytosis complex could modulate nuclear internalization of Tat peptides.
Tat 肽介导生物分子的核内化提供了一种将药物递送至细胞的机制。然而，分子成像探针向细胞核的转运可能会诱发不良的诱变作用。为了评估在不发生核转运的情况下保留其细胞渗透效应的可行性，将 Tat 肽与生长抑素受体（STR）亲和配体（Oct）偶联，并标记荧光染料。结果表明，Tat-Oct-5-FAM（荧光素 5'-羧酸）保留在 STR 阳性 AR42J 细胞的细胞质中。Tat-Oct-5-FAM 与 ATP 共同孵育可诱导核转运。这些数据表明，染料和 Oct-STR 内吞复合物均可调节 Tat 肽的核内化。
