Transporter peptide を用いた機能性ペプチド/タンパク導入系の構築と細胞内分子標的療法への応用 Transport system for the biologically active peptides/proteins into mammalian cells with transporter peptide

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著者

    • 近藤 英作 KONDO Eisaku
    • 岡山大学大学院医歯薬学総合研究科 病理病態学分野 Department of Pathology, Okayama University Graduate School of Medicine and Dentistry
    • 瀬戸 加大 SETO Masao
    • 愛知県がんセンター研究所 遺伝子医療研究部 Division of Molecular Medicine, Aichi Cancer Center Research Institute
    • 上田 龍三 UEDA Ryuzo
    • 名古屋市立大学大学院医学研究科臨床分子内科学 Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences
    • 吉野 正 YOSHINO Tadashi
    • 岡山大学大学院医歯薬学総合研究科 病理病態学分野 Department of Pathology, Okayama University Graduate School of Medicine and Dentistry

抄録

<p>Molecular targeting of hematopoietic malignancies has not been successfully developed because of difficulties in introducing genes of interest into these neoplastic cells. Recently, peptide delivery systems using protein transduction domains (PTD) have attracted attention for possibly overcoming such obstacles in a therapeutic approach. Here, we show the development of a peptide transporter system of maximum utility that can suppress growth of biologically aggressive or intractable leukemia/lymphoma cells. The transporter (Wr- T) has an enlarged hydrophobic pocket consisting of triple tryptophan-rich domains fused with nine D-enantiomer poly-arginines (D-Arg) via proline spacers, which enhance the efficiency of peptide-introduction over previous mechanisms by more than 20 times. Delivering small amounts of p16 (INK4a) functional peptide by Wr-T enables dramatic inhibition of growth of up to 80% in highly aggressive leukemia/lymphomas lacking p16 expression by recovery of their p16 function. Thus, the WR-T system exhibits high-performance cargopeptide delivery and is supposed to be useful for treating hematopoietic malignancies in combination of the p16 peptide. This system may also help treat various tumors by functional peptide selection.</p>

収録刊行物

  • Cytometry research = 日本サイトメトリー学会機関誌

    Cytometry research = 日本サイトメトリー学会機関誌 16(2), 25-32, 2006-09-25

    日本サイトメトリー学会

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