Transport system for the biologically active peptides/proteins into mammalian cells with tranporter peptide

DOI 13 References
  • Yoshikawa Kazuhiro
    Department of Pathology, Aichi Medical University School of Medicine, Aichi, Japan
  • Kondo Eisaku
    Department of Pathology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan
  • Seto Masao
    Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan
  • Saga Shinsuke
    Department of Pathology, Aichi Medical University School of Medicine, Aichi, Japan
  • Ueda Ryuzo
    Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
  • Takahashi Toshitada
    Aichi Cancer Center, Nagoya, Japan
  • Yoshino Tadashi
    Department of Pathology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan

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  • 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

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Abstract

<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>

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