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2013 Fiscal Year Final Research Report

Development of neo-biologics targeted on protein-protein interaction sites

Research Project

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Project/Area Number 23390140
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied pharmacology
Research InstitutionThe University of Tokushima

Principal Investigator

ITOH Kohji  徳島大学, ヘルスバイオサイエンス研究部, 教授 (00184656)

Co-Investigator(Kenkyū-buntansha) HIROKAWA Takatsugu  産業技術総合研究所, 生命情報工学研究センター, 研究チーム長 (20357867)
Project Period (FY) 2011-04-01 – 2014-03-31
Keywordsリソソーム酵素 / 酵素補充療法 / ケミカルシャペロン / 疾患特異的iPS細胞 / 酵素増強薬 / リソソーム病 / in silicoデザイン / トランスジェニックカイコ
Research Abstract

To develop novel therapeutics for human deficiencies (lysosomal storage diseases) of lysosomal cathepsin A (CathA) and neuraminidase-1 (NEU1) based on protein-protein interaction between CathA and NEU1, we produced transgenic (Tg) silkworm strains overexpressing human CathA and NEU1 in middle silk glands, and succeeded in purification and elucidation of X-ray crystal structure of the enzymatically active CathA. The conjugates of active CathA purified from Tg silk glands and cell-penetrating peptides (R8) had replacement effects on cultured fibroblasts derived from patients with CathA deficiency (Galactosialidosis) to reduce the accumulated sialyloligosaccharides. In addition, siastatin B was found to have stabilizing effects like a chaperone compound on recombinant human cytosolic NEU2 with structural similarity to NEU1.

  • Research Products

    (12 results)

All 2014 2013 2011 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (3 results) Book (2 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Inhibitory effects and specificity of synthetic sialyldendrimers toward recombinant human cytosolic sialidase 2 (NEU2)2013

    • Author(s)
      M.M. Rahman, S. Kitao, D. Tsuji, K. Suzuki, K. Matsuoka, F. Matsuzawa, S. Aikawa, K. Itoh
    • Journal Title

      Glycobiol

      Volume: 23 Pages: 495-504

    • DOI

      10.1093/glycob/cws221

    • Peer Reviewed
  • [Journal Article] Chemical synthesis of biologically active monoglycosylated GM2-activator protein analog using N-sulfanylethylanilide peptide2013

    • Author(s)
      K. Sato, A. Shigenaga, K. Kitakaze, K. Sakamoto, D. Tsuji, K. Itoh, A. Otaka
    • Journal Title

      Angew. Chem. Int. Ed

      Volume: 52 Pages: 7855-7859

    • DOI

      10.1002/anie.201303390

    • Peer Reviewed
  • [Journal Article] Modeling of Human Neuraminidase-1 and Its Validation by LERE-Correlation Analysis2013

    • Author(s)
      S. Hitaoka, Y. Shibata, H. Matoba, A. Kawano, M. Harada, M.M. Rahman, D. Tsuji D, T. Hirokawa, K. Itoh, T.Yoshida, H. Chuman
    • Journal Title

      Chem-Bio Informatics Journal

      Volume: 13 Pages: 30-44

    • DOI

      10.1273/cbij.13.30

    • Peer Reviewed
  • [Journal Article] Therapeutic potential of intracellular replacement of modified human beta-hexosaminidase B for GM2 gangliosidosis2011

    • Author(s)
      K. Matsuoka, T. Tamura, D. Tsuji, Y. Dohzono, K. Kitakaze, S. Saito, H. Sakuraba, and K. Itoh
    • Journal Title

      Mol. Ther

      Volume: 19 Pages: 1017-1024

    • DOI

      10.1038/mt.2011.27

    • Peer Reviewed
  • [Journal Article] Highly phosphomannosylated enzyme replacement therapy for GM2 gangliosidosis2011

    • Author(s)
      D. Tsuji, H. Akeboshi, K. Matsuoka, H. Yasuoka, E. Miyasaki, Y. Kasahara, I. Kawashima, Y. Chiba, Y. Jigami, T. Taki, H. Sakuraba, and K. Itoh
    • Journal Title

      Ann. Neurol

      Volume: 69 Pages: 691-701

    • DOI

      10.1002/ana.22262

    • Peer Reviewed
  • [Presentation] Establishment of patient-derived iPS cells with neurodegenerative lysosomal storage diseases and application for evaluating lysosomal enzyme replacement effects on differentiated neural cells2014

    • Author(s)
      K. Itoh, D. Tsuji, M. Ikuo, K. Kitakaze, S. Nishioka, I. Imataki, S. Yamaguchi, Y. Chiba, H. Sakuraba, I. Kobayashi, H. Sezutsu, H. Machii
    • Organizer
      The IUBMB 10th International Symposium on Cell Surface Macromolecules, Saha ainstitute of Nuclear, Kolkata
    • Place of Presentation
      Kolkata(India)
    • Year and Date
      20140120-24
  • [Presentation] ネオバイオロジクスの創製とリソソーム病治療薬開発へのアプローチ2013

    • Author(s)
      伊藤孝司
    • Organizer
      第5回全国共同利用・共同開発「酵素学研究拠点」シンポジウム
    • Place of Presentation
      千里ライフサイエンスセンター(大阪府)
    • Year and Date
      2013-11-23
  • [Presentation] Molecular properties of recombinant human lysosomal enzyme produced by transgenic silkworm and therapeutic potential for lysosomal storage disease2013

    • Author(s)
      K. Itoh, D. Tsuji, S. Nishioka, S. Ikedo, T. Higashi, I. Kobayashi, H. Sezutsu, A. Ishii, K. Harazono, M. Tada, N. Kawasaki, H. Machii
    • Organizer
      Gordon Research Conference (Lysosomal Diseases)
    • Place of Presentation
      Lucca, Barga(Italy)
    • Year and Date
      2013-04-14
  • [Book] Molecular Therapy for Lysosomal Storage Diseases2013

    • Author(s)
      Tsuji, D., Itoh, K
    • Total Pages
      745(591-607)
    • Publisher
      InTech in Gene Therapy - Tools and Potential Applications
  • [Book] 「ガラクトシアリドーシス」先天代謝異常ハンドブック2013

    • Author(s)
      伊藤孝司
    • Total Pages
      456(214-215)
    • Publisher
      中山書店
  • [Remarks] 東哲也「リソソーム性Neuraminidase-1 (NEU1)のin cell 結晶化」第54回日本生化学会中国・四国支部例会学術奨励賞(学生)2013年5月

  • [Patent(Industrial Property Rights)] ベンジルアミン誘導体2011

    • Inventor(s)
      辻大輔, 伊藤孝司, 大高章重永章
    • Industrial Property Rights Holder
      徳島大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      特願2011-119668
    • Filing Date
      2011-05-27
    • Overseas

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Published: 2015-06-25  

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