Improved cytosolic translocation and tumor-killing activity of Tat-shepherdin conjugates mediated by co-treatment with Tat-fused endosome-disruptive HA2 peptide

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• 作者：Toshiki Sugita ; Tomoaki Yoshikawa ; Yohei Mukai ; Natsue Yamanada ; Sunao Imai ; Kazuya Nagano ; Yasunobu Yoshida ; Hiroko Shibata ; Yasuo Yoshioka ; Shinsaku Nakagawa ; Haruhiko Kamada ; Shin-ichi Tsunoda ; Ya
• 关键词：Tat ; HA2 ; Protein transduction domain ; PTD ; Shepherdin ; Peptidomimetic antagonist ; Peptide blocker
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2007
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：30 November 2007
• 卷：363
• 期：4
• 页码：1027-1032
• 文件大小：390 K

摘要

Tat peptides are useful carriers for delivering biologic molecules into the cell for both functional analysis of intracellular disease-related proteins and treatment of refractory diseases. Most internalized Tat-fused cargos (Tat-cargos) are trapped within the endosome, however, which limits the biologic function of the cargo. In this study, we demonstrated that Tat-fused HA2 peptide (HA2^Tat), an endosome disrupted peptide, enhanced the endosome-escape efficiency of Tat-cargos. In cells treated with a mixture of fluorescein isothiocyanate-labeled Tat and HA2^Tat, widespread fluorescence was observed throughout the cytosol. In addition, this HA2^Tat-mediated cytosolic delivery technique led to enhanced cytotoxicity of Tat-fused anti-cancer peptides, specifically shepherdin. Thus, we improved the function of the delivered molecules by co-treating with HA2^Tat and propose that this is a useful method for the delivery of therapeutic macromolecules into the cytosol.