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  • Title: Improved cytosolic translocation and tumor-killing activity of Tat-shepherdin conjugates mediated by co-treatment with Tat-fused endosome-disruptive HA2 peptide.
    Author: Sugita T, Yoshikawa T, Mukai Y, Yamanada N, Imai S, Nagano K, Yoshida Y, Shibata H, Yoshioka Y, Nakagawa S, Kamada H, Tsunoda S, Tsutsumi Y.
    Journal: Biochem Biophys Res Commun; 2007 Nov 30; 363(4):1027-32. PubMed ID: 17923117.
    Abstract:
    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 (HA2Tat), an endosome disrupted peptide, enhanced the endosome-escape efficiency of Tat-cargos. In cells treated with a mixture of fluorescein isothiocyanate-labeled Tat and HA2Tat, widespread fluorescence was observed throughout the cytosol. In addition, this HA2Tat-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 HA2Tat and propose that this is a useful method for the delivery of therapeutic macromolecules into the cytosol.
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