Development of neo-biologics targeted on protein-protein interaction sites
Project/Area Number |
23390140
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Applied pharmacology
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Research Institution | The 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)
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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
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Project Status |
Completed (Fiscal Year 2013)
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Budget Amount *help |
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2013: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2012: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2011: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
|
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 / ドラックデリバリー / 組換えカイコ / タンパク間相互作用 / iPS細胞 / ドラッグデリバリー |
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.
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Report
(4 results)
Research Products
(124 results)
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[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
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Journal Title
Chem-Bio Informatics Journal
Volume: 13
Issue: 0
Pages: 30-44
DOI
NAID
ISSN
1347-0442, 1347-6297
Related Report
Peer Reviewed
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[Journal Article] Combination with a defucosylated anti-HM1.24 monoclonal antibody plus lenalidomide induces marked ADCC against myeloma cells and their progenitors2013
Author(s)
T. Harada, S. Ozaki, A. Oda, D. Tsuji, A. Ikegame, M. Iwasa, K. Udaka, S. Fujii, S. Nakamura, H. Miki, K. Kagawa, Y. Kuroda, S. Kawai, K. Itoh, H. Yamada-Okabe, T. Matsumoto, M. Abe
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Journal Title
PLoS One
Volume: vol.26; 8(12)
Issue: 12
Pages: e83905-e83905
DOI
Related Report
Peer Reviewed
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[Journal Article] Highly phosphomannosylated enzyme replacement therapy for GM2 gangliosidosis2011
Author(s)
Tsuji D, Akeboshi H, Matsuoka K, Yasuoka H, Miyasaki E, Kasahara Y, Kawashima I, Chiba Y, Jigami Y, Taki T, Sakuraba H, Itoh K
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Journal Title
Ann Neurol
Volume: 69
Issue: 4
Pages: 691-701
DOI
Related Report
Peer Reviewed
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[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)
Related Report
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[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
Related Report
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[Presentation] ヒトノイラミニダーゼ-シアル酸誘導体複合体相互作用の非経験的フラグメント分子軌道法計算に基づく相関解析(LERE-QSAR)2011
Author(s)
比多岡清司, 的場弘, 原田政隆, 河野明大, 坂本修平, 岡田耕平, 吉田達貞, 辻大輔, 広川貴次, 伊藤孝司, 中馬寛
Organizer
第39回構造活性相関シンポジウム
Place of Presentation
東京都(東京理科大学薬学部)
Year and Date
2011-11-28
Related Report
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[Presentation] Establishment of patient-derived iPS cells with neurodegenerative lysosomal storage diseases and application for evaluating lysosomal enzyme replacement effects on differentiated neural cells.
Author(s)
Kouji Itou, Daisuke Tsuji, Mariko Ikuo, Keisuke Kitakaze, So-ichirou Nishioka, Izumi Imataki, Saeka Yamaguchi, Yasunori Chiba, Hitoshi Sakuraba, Isao Kobayashi, Hideki Sezutsu and Hiroaki Machii
Organizer
The IUBMB 10th International Symposium on Cell Surface Macromolecules
Place of Presentation
Saha Institute of Nuclear Physics,Kolkata(India)
Related Report
Invited
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[Presentation] Molecular properties of recombinant human lysosomal enzyme produced by transgenic silkworm and therapeutic potential for lysosomal storage disease.
Author(s)
Kouji Itou, Daisuke Tsuji, So-ichirou Nishioka, Syunsuke Ikedo, Tetuya Higashi, I Kobayashi, H Sezutsu, A Ishii, K. Harazono, M. Tada, Nana Kawasaki and Hiroaki Machii
Organizer
Gordon Research Conference 2013 Lysosomal Diseases
Place of Presentation
Renaissance Tuscany Il Ciocco Resort ,Lucca(Italy)
Related Report
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[Presentation] メタノール資化性酵母発現系を用いた組換えマンノース6リン酸受容体の精製とその応用
Author(s)
西岡 宗一郎, 小林 功, 辻 大輔, 池戸 駿介, Md.RAHMAN Motiur, 東 哲也, 真板 宣夫, 瀬筒 秀樹, 町井 博明, 原園 景, 石井 明子, 川崎 ナナ, 伊藤 孝司
Organizer
第52回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会
Place of Presentation
愛媛大学(愛媛県)
Related Report
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[Presentation] GM2ガングリオシド蓄積症モデルマウス由来単球系細胞におけるアクチン重合系と浸潤性の変動
Author(s)
幾尾 真理子, 齋藤 裕樹, 大前 陽輔, 毛 瀚, 長野 源太郎, 藤幸 知子, 沼田 俊介, 韓 笑, 小幡 佳津明, 長谷川 節雄, 山口 博樹, 猪口 孝一, 伊藤 輝代, 平松 啓一, 伊藤 孝司, 関水 和久, 垣内 力
Organizer
第86回日本生化学会大会
Place of Presentation
パシフィコ横浜(神奈川県)
Related Report
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[Presentation] ガラクシアリドーシス治療薬候補としてのトランスジェニックカイコ由来ヒトカテプシンAの解析
Author(s)
西岡 宗一郎, 小林 功, 辻 大輔, 池戸 駿介, Md.RAHMAN Motiur, 東 哲也, 真板 宣夫, 瀬筒 秀樹, 町井 博明, 原園 景, 石井 明子, 川崎 ナナ, 伊藤 孝司
Organizer
第86回日本生化学会大会
Place of Presentation
パシフィコ横浜(神奈川県)
Related Report
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[Presentation] バイオ医薬品の生産基材としてのトランスジェニックカイコとネオグライコバイオロジクス創製への応用
Author(s)
伊藤 孝司, 小林 巧, 西岡 宗一郎, 原園 景, 久保 勇樹, 真板 宣夫, 辻 大輔, Md Motiiur RAHMAN, 池戸 駿介, 石井 明子, 川崎 ナナ, 町井 博明, 瀬筒 秀樹
Organizer
第32回日本糖質学会大会
Place of Presentation
大阪国際交流センター ( 大阪府)
Related Report
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[Presentation] ガラクシアリドーシス治療薬候補としてのトランスジェニックカイコ由来ヒトカテプシンAの解析
Author(s)
西岡 宗一郎, 小林 功, 辻 大輔, 池戸 駿介, Md.RAHMAN Motiur, 東 哲也, 真板 宣夫, 瀬筒 秀樹, 町井 博明, 原園 景, 石井 明子, 川崎 ナナ, 伊藤 孝司
Organizer
第54回日本生化学会中国・四国支部例会
Place of Presentation
徳島大学(徳島県)
Related Report
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