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Translational research on a drug delivery system using substrate binding domain derived from bacterial collagenases

Research Project

Project/Area Number 20590452
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionKitasato University

Principal Investigator

MATSUSHITA Osamu  Kitasato University, 医学部, 教授 (00209537)

Co-Investigator(Kenkyū-buntansha) KOIDE Takaki  早稲田大学, 先進理工学部, 教授 (70322253)
TAMAI Eiji  松山大学, 薬学部, 准教授 (40333512)
MIYATA Shigeru  香川大学, 医学部, 講師 (90314913)
Co-Investigator(Renkei-kenkyūsha) MIMAMI Junzaburo  香川県立保健医療大学, 保健医療学部, 教授 (40157566)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywordsガス壊疽菌群 / 毒素 / 構造活性相関 / コラーゲン結合ドメイン / 成長因子 / 骨新生 / 鼓膜閉鎖術 / 人工皮膚 / コラゲナーゼ / 上皮細胞成長因子 / 鼓膜穿孔 / 血管内皮細胞成長因子 / 血管新生 / 再生医療 / スピン標識ペプチド / 表皮成長因子 / 重層扁平上皮
Research Abstract

'Flesh-eating bacteria' produce collagenases to hydrolyze collagen fibrils in tissue. These enzymes possess domain(s) to bind to this insoluble substrate (CBD). We identified amino acid residues responsible for the binding. We also showed that CBD binds preferentially to the under-wound region in the collagen molecule, and that the binding is unidirectional. Ca^<2+> binds to the linker region of CBD. We showed that the binding modifies CBD into a more stable and more efficient conformation. Finally, we showed the potential benefits of matrix anchoring of various bioactivity substances using CBD, which are applicable to various therapies in regenerative medicine.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (29 results)

All 2011 2010 2009 2008 Other

All Journal Article (11 results) (of which Peer Reviewed: 11 results) Presentation (10 results) Remarks (2 results) Patent(Industrial Property Rights) (6 results) (of which Overseas: 2 results)

  • [Journal Article] Monthly administration of a novel PTH-vollagen binding domain fusion protein is anabolic in mice. Calcif.2011

    • Author(s)
      Ponnapakkam T., Katikaneni, R., Miller, E., Ponnapakkam, A., Suda, H., Miyata, S., Suva, L.J., JSakon, J., Matsushita, O., Gensure, R.C.
    • Journal Title

      Tissue Int. in press

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Development of a high-throughput screening system for the compounds that inhibit collagen-protein interactions.2009

    • Author(s)
      Okano-Kosugi, H., Matsushita, O., Asada, S., Herr, A.B., Kitagawa, K., Koide, T.
    • Journal Title

      Anal.Biochem. 394

      Pages: 125-131

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ca2^+-induced linker transformation leads to a compact and rigid collagen-binding domain of Clostridium histolyticum collagenase.2009

    • Author(s)
      Philominathan, S.T., Matsushita, O., Gensure, R., Sakon, J.
    • Journal Title

      FEBS J. 276

      Pages: 3589-3601

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Unidirectional binding of clostridial collagenase to triple helical substrates.2009

    • Author(s)
      Philominathan, S.T., Koide, T., Hamada, K., Yasui, H., Seifert, S., Matsushita, O., Sakon, J.
    • Journal Title

      J.Biol.Chem. 284

      Pages: 10868-10876

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Unidirectional binding of clostridial collagenase to triple helical substrates.2009

    • Author(s)
      Philominathan ST, Koide T, Hamada K, Yasui H, Seifert S, Matsushita O, Sakon J.
    • Journal Title

      J.Biol.Chem. 284

      Pages: 10868-10876

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ca^<2+>-induced linker transformation leads to a compact and rigid collagen-binding domain of Clostridium histolyticum collagenase.2009

    • Author(s)
      Philominathan ST, Matsushita O, Gensure R, Sakon J.
    • Journal Title

      FEBS J. 276

      Pages: 3589-3601

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of a high-throughput screening system for the compounds that inhibit collagen-protein interactions.2009

    • Author(s)
      Okano-Kosugi H, Matsushita O, Asada S, Herr AB, Kitagawa K, Koide T.
    • Journal Title

      Anal.Biochem. 394

      Pages: 125-131

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 1H, 13C and 15N resonace assignments of Ca2^+-bound collagen-binding domain derived from a clostridial collagenase.2008

    • Author(s)
      Philominathan, S.T.L., Matsushita, O., Jordan, J.B., Sakon, J.
    • Journal Title

      Biomol.NMR Assign. 2

      Pages: 127-129

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] High-level expression of his-tagged clostridial collagenase in Clostridium perfringens.2008

    • Author(s)
      Tamai, E., Miyata, S., Tanaka, H., Nariya, H., Suzuki,M., Matsushita, O., Hatano, N., Okabe, A.
    • Journal Title

      Appl.Microbiol.Biotechnol. 80

      Pages: 627-635

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] High-level expression of his-tagged clostridial collagenase in Clostridium perfringens.2008

    • Author(s)
      Tamai, E., Miyata, S., Tanaka, H., Nariya, H., Suzuki, M., Matsushita, O., Hatano, N., Okabe, A.
    • Journal Title

      Appl. Microbiol. Biotechnol. 80

      Pages: 627-635

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ^1H,^<13>C and ^<15>N resonace assignments of Ca^<2+> bound collagen-binding domain derived from a clostridial collagenase2008

    • Author(s)
      Philominathan, S. T. L., Matsushita, O., Jordan, J. B., Sakon, J.
    • Journal Title

      Biomol. NMR Assign. 2

      Pages: 127-129

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] From bacterial toxin to drug.2010

    • Author(s)
      Matsushita O., Collagen anchoring
    • Organizer
      11th Joint Symposium Robert Koch Institute and The Kitasato Institute Kitasato University
    • Place of Presentation
      東京都港区
    • Year and Date
      2010-10-26
    • Related Report
      2010 Final Research Report
  • [Presentation] Collagen anchoring : From bacterial toxin to drug2010

    • Author(s)
      Osamu Matsushita
    • Organizer
      11th Joint Symposium Robert Koch Institute and The Kitasato Institute Kitasato University
    • Place of Presentation
      北里大学薬学部コンベンションホール(東京都)
    • Year and Date
      2010-10-26
    • Related Report
      2010 Annual Research Report
  • [Presentation] ガス壊疽菌群コラゲナーゼの基質結合ドメインと再生医療への応用2010

    • Author(s)
      松下治、西望、小杉日登美、小出隆規、安達栄治郎、坂本恵子、服部雅一
    • Organizer
      第57回トキシンシンポジウム
    • Place of Presentation
      滋賀県長浜市
    • Year and Date
      2010-07-16
    • Related Report
      2010 Final Research Report
  • [Presentation] ガス壊疽菌群コラゲナーゼの基質結合ドメインと再生医療への応用2010

    • Author(s)
      松下治、西望、小杉日登美、小出隆規、安達栄治郎、坂本恵子、服部雅一
    • Organizer
      第57回トキシンシンポジウム
    • Place of Presentation
      長浜ロイヤルホテル(滋賀県)
    • Year and Date
      2010-07-16
    • Related Report
      2010 Annual Research Report
  • [Presentation] コラーゲン結合ドメインの構造解析と薬物送達システムへの応用2010

    • Author(s)
      松下治、宮田茂
    • Organizer
      第83回日本細菌学会
    • Place of Presentation
      神奈川県横浜市
    • Year and Date
      2010-03-27
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] ガス壊疽菌群コラゲナーゼの基質結合様式と積層型人工組織作製への応用2009

    • Author(s)
      松下治
    • Organizer
      第56回トキキンシンポジウム
    • Place of Presentation
      岐阜県岐阜市
    • Year and Date
      2009-08-27
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] Substrate recognition of collagen-binding domains derived from bacterial collagenases.2009

    • Author(s)
      Matsushita O., Nishi N., Koide T., Philominathan S.T.L., Sakon J., Gensure R.C., Iwashiro H., Adachi E.
    • Organizer
      8th Pan-pacific connective tissue societies symposium, 41st Annual meeting of the Japanese society of connective tissue research, 56th Annual meeting of the Japan matrix club
    • Place of Presentation
      神奈川県逗子市
    • Year and Date
      2009-06-04
    • Related Report
      2010 Final Research Report
  • [Presentation] Substrate recognition of collagen-binding domains derived from bacterial collagenases2009

    • Author(s)
      Matsushita O, Nishi N, Koide T, Philominathan STL, Sakon J Gensure RC, Iwashiro H, Adachi E
    • Organizer
      8th Pan-pacific connective tissue societies symposium, 41st Annual meeting of the Japanese society of connective tissue research, 56th Annual meeting of the Japan matrix club
    • Place of Presentation
      神奈川県逗子市
    • Year and Date
      2009-06-04
    • Related Report
      2009 Annual Research Report
  • [Presentation] ガス壊疽菌群コラゲナーゼの基質認識機構と再生医学への応用2009

    • Author(s)
      松下治、小出隆規、安達栄治郎
    • Organizer
      第82回日本細菌学会総会
    • Place of Presentation
      愛知県名古屋市
    • Year and Date
      2009-03-12
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] ガス壊疽菌群コラゲナーゼのセグメント2の構造解析2008

    • Author(s)
      松下治
    • Organizer
      第91回日本細菌学会関東支部総会
    • Place of Presentation
      千葉県長生郡長塚町
    • Year and Date
      2008-10-23
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Remarks] ホームページ等

    • URL

      http://web.med.kitasato-u.ac.jp/edures/microbio/toxin.html

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://web.med.kitasato-u.ac.jp/edures/microbio/toxin.html

    • Related Report
      2010 Annual Research Report
  • [Patent(Industrial Property Rights)] 粘膜、上皮および鼓膜の少なくとも一つの再生材および再生評価方法2010

    • Inventor(s)
      宮下武憲、森望、西望、安達栄治郎、松下治、服部雅一、伊藤周平、坂本恵子
    • Industrial Property Rights Holder
      国立大学法人香川大学、学校法人北里研究所
    • Industrial Property Number
      2010-110694
    • Filing Date
      2010-05-12
    • Related Report
      2010 Final Research Report
  • [Patent(Industrial Property Rights)] 積層型高密度培養人工組織の製造方法及び積層型高密度培養人工組織2010

    • Inventor(s)
      安達栄治郎、松下治、岩城啓修、細谷智、西望
    • Industrial Property Rights Holder
      学校法人北里研究所、国立大学法人香川大学
    • Filing Date
      2010-01-28
    • Related Report
      2010 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 粘膜、上皮および鼓膜の少なくとも-つの再生材および再生評価方法2010

    • Inventor(s)
      宮下武憲、森望、西望、安達栄治郎、松下治、服部雅一、伊藤周平、坂本恵子
    • Industrial Property Rights Holder
      香川大学 北里大学
    • Industrial Property Number
      2010-110694
    • Filing Date
      2010-05-12
    • Related Report
      2010 Annual Research Report
  • [Patent(Industrial Property Rights)] 積層型高密度培養人工組織の製造方法及び積層型高密度培養人工組織2010

    • Inventor(s)
      安達栄治郎、松下治、岩城啓修、細谷智、西望
    • Industrial Property Rights Holder
      学校法人北里研究所・国立大学法人香川大学
    • Filing Date
      2010-01-28
    • Related Report
      2009 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 積層型高密度培養人工組織の製造方法及び積層型高密度培養人工組織2009

    • Inventor(s)
      安達栄治郎、松下治、岩城啓修、細谷智、西望
    • Industrial Property Rights Holder
      学校法人北里研究所、国立大学法人香川大学
    • Industrial Property Number
      2009-017475
    • Filing Date
      2009-01-19
    • Related Report
      2010 Final Research Report
  • [Patent(Industrial Property Rights)] 積層型高密度培養人工組織の製造方法及び積層型高密度培養人工組織2009

    • Inventor(s)
      安達栄治郎, 松下治, 岩城啓修, 細谷 智, 西 望
    • Industrial Property Rights Holder
      学校法人北里研究所, 国立大学法人香川大学
    • Industrial Property Number
      2009-017475
    • Filing Date
      2009-01-19
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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