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Mechanism analysis of sulfobetaines' activity to prevent protein aggregation and application of sulfobetaines to unstable proteins

Research Project

Project/Area Number 21570108
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Structural biochemistry
Research InstitutionGunma University

Principal Investigator

WAKAMATSU Kaori  群馬大学, 大学院・工学研究科, 教授 (40222426)

Co-Investigator(Renkei-kenkyūsha) SUGASE Kenji  (財)サントリー生物有機科学研究所, 主席研究員 (00300822)
NAMEKI Nobukazu  群馬大学, 大学院・工学研究科, 准教授 (80302959)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsタンパク質 / 凝集防止 / 安定化 / スルホベタイン / メカニズム / 運動性 / オスモライト / 分子サイズ / 溶解度 / 凝集 / 変性 / 抗体 / 精製 / 収率 / 効率化 / 構造多型 / NMR / NDSB / 立体構造解析
Research Abstract

Aggregation of proteins brings about severe problems in drug development. Although sulfobetaines have been known to prevent protein aggregation, its mechanisms have been elusive. Here we found that sulfobetaines accelerate inter-conformer exchange rates of proteins and increase flexibility of loops. In addition, sulfobetaines were found to make proteins unstable depending on the identity of proteins and buffer conditions. Prevention of protein aggregation by sulfobetaines did not correlate with enhancement of thermostability of proteins. Sulfobetaines were found to be useful for protecting antibodies and for efficient purification of unstable proteins.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (43 results)

All 2012 2011 2010 2009 Other

All Journal Article (19 results) (of which Peer Reviewed: 19 results) Presentation (23 results) Remarks (1 results)

  • [Journal Article] Inhibitory effects of choline-O-sulfate on amyloid formation of human islet amyloid polypeptide2012

    • Author(s)
      M. Hagihara, A. Takei, T. Ishii, F. Hayashi, K. Kubota, K. Wakamatsu, N. Nameki
    • Journal Title

      FEBS Open Bio

      Volume: 2 Pages: 20-25

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Additive effects of betaines on the fibrinogen cryogelation induced by low temperature2011

    • Author(s)
      Y. Toyama, K. Miyamoto, K. Kubota, K. Wakamatsu, N. Nobukazu, T. Saheki, M. Ochiai
    • Journal Title

      Trans. Materials Res. Soc. J.

      Volume: 36 Pages: 393-396

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Fucose content of monoclonal antibodies can be controlled by culture medium osmolality for high antibody-dependent cellular cytotoxicity2011

    • Author(s)
      Y. Konno, Y. Kobayashi, K. Takahashi, E. Takahashi, S. Sakae, M. Wakitani, K. Yamano, T. Suzawa1, K. Yano, T. Ohta, M. Koike, K. Wakamatsu, S. Hosoi
    • Journal Title

      Cytotechmology

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of the aggregation states of monoclonal antibodies by diverse and complementary methods2011

    • Author(s)
      T. Yoshino, T. Ishikawa, T. Ishihara, Y. Takeuchi, H. Yoshikawa, H. Yoshida, H. Yoshida, K. Wakamatsu
    • Journal Title

      Biol. Pharm. Bull.

      Volume: 34 Pages: 1273-1278

    • NAID

      130000936598

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Enhancement of antibody production by the addition of Coenzyme-Q_<10>2011

    • Author(s)
      Y. Konno, M. Aoki, M. Takagishi, N. Sakai, M. Koike, K. Wakamatsu, S. Hosoi
    • Journal Title

      Cytotechnology

      Volume: 63 Pages: 163-170

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Additive effects of betaines on the fibrinogen cryogelation induced by low temperature2011

    • Author(s)
      Y.Toyama, K.Miyamoto, K.Kubota, K.Wakamatsu, N.Nobukazu, T.Saheki, M.Ochiai
    • Journal Title

      Trans.Materials Res.Soc.J.

      Volume: 36 Pages: 393-396

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhancement of antibody production by the addition of Coenzyme-Q(10)2011

    • Author(s)
      Y.Konno, M.Aoki, M.Takagishi, N.Sakai, M.Koike, K.Wakamatsu, S.Hosoi
    • Journal Title

      Cytotechnology

      Volume: 63 Pages: 163-170

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Influence of pH on Heat-Induced Aggregation and Degradation of Therapeutic Monoclonal Antibodies2010

    • Author(s)
      T. Ishikawa, T. Ito, R. Endo, K. Nakagawa, E. Sawa, K. Wakamatsu
    • Journal Title

      Biol. Pharm. Bull.

      Volume: 33 Pages: 1413-1417

    • NAID

      130000300369

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Relationship between human IgG structure and retention time in hydroxyapatite chromatography with sodium-chloride gradient elution2010

    • Author(s)
      T. Nakagawa, T. Ishihara, H. Yoshida, T. Yoshida, K. Wakamatsu, T. Kadoya
    • Journal Title

      J. Sep. Sci.

      Volume: 33 Pages: 2045-2051

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prevention of stirring-induced microparticle formation in monoclonal antibody solutions2010

    • Author(s)
      T. Ishikawa, N. Kobayashi, C. Osawa, E. Sawa, K. Wakamatsu
    • Journal Title

      Biol. Pharm. Bull.

      Volume: 33 Pages: 1043-1046

    • NAID

      130000247976

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Relationship between human IgG structure and retention time in hydroxyapatite chromatography with sodium-phosphate gradient elution2010

    • Author(s)
      T. Nakagawa, T. Ishihara, H. Yoshida, T. Yoneya, K. Wakamatsu, T. Kadoya
    • Journal Title

      J. Sep. Sci.

      Volume: 33 Pages: 37-45

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Relationship between human IgG structure and retention time in hydro xyapatite chromatography with sodium-chloride gradient elution2010

    • Author(s)
      T.Nakagawa, T.Ishihara, H.Yoshida, T.Yoshida, K.Wakamatsu, T.Kadoya
    • Journal Title

      J. Sep. Sci.

      Volume: 33 Pages: 2045-2051

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Influence of pH on Heat-Induced Aggregation and Degradation of Thera peutic Monoclonal Antibodies2010

    • Author(s)
      T.Ishikawa, T.Ito, R.Endo, K.Nakagawa, E.Sawa, K.Wakamatsu
    • Journal Title

      Biol. Pharm. Bull.

      Volume: 33 Pages: 1413-1417

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Binding site of C-reactive protein on M-ficolin2009

    • Author(s)
      M. Tanio, K. Wakamatsu, T. Kohno
    • Journal Title

      Mol Immunol.

      Volume: 47 Pages: 215-221

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] GDP-GTP exchange processes of G・i1 proten areaccelrated/decelerted depending on the type and the concentration of added detergents2009

    • Author(s)
      M. Kubota, T. Tanaka, T. Kohno, K. Wakamatsu
    • Journal Title

      J. Biochem

      Volume: 146 Pages: 875-880

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] GDP-GTP exchange processes of Goil protein are accelerated/decelerated depending on the type and the concentration of added detergents2009

    • Author(s)
      M.Kubota, T.Tanaka, T.Kohno, K.Wakamatsu
    • Journal Title

      J.Biochem. 146

      Pages: 875-880

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Binding site of C-reactive protein on M-ficolin2009

    • Author(s)
      M.Tanio, K.Wakamatsu, T.Kohno
    • Journal Title

      Mol.Immunol. 47

      Pages: 215-221

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Relationship between human IgG structure and retention time in hydroxyapatite chromatography with sodium-phosphate gradient elution

    • Author(s)
      T.Nakagawa, T.Ishihara, H.Yoshida, T.Yoneya, K.Wakamatsu, T.Kadoya
    • Journal Title

      J.Sep.Sci. (印刷中)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prevention of stirring-induced microparticle formation in monoclonal antibody solutions

    • Author(s)
      T.Ishikawa, N.Kobayashi, C.Osawa, E.Sawa, K.Wakamatsu
    • Journal Title

      Biol.Pharm.Bull. (印刷中)

    • NAID

      130000247976

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] NDSBによるタンパク質の凝集防止のメカニズムと応用2011

    • Author(s)
      吉澤光彦, 王海梅, 白澤豊, 野城真芳, 稲岡斉彦, 寺脇慎一, 若松馨
    • Organizer
      平成23年度日本化学会関東支部群馬地区地域懇談会
    • Place of Presentation
      群馬大学工学部桐生キャンパス
    • Year and Date
      2011-12-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] シアーストレスが引き起こす蛋白質凝集のスルホベタインによる防止2011

    • Author(s)
      出村哲朗, 中沢和磨, 外山吉治, 寺脇慎一, 若松馨
    • Organizer
      平成23年度日本化学会関東支部群馬地区地域懇談会
    • Place of Presentation
      群馬大学工学部桐生キャンパス
    • Year and Date
      2011-12-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] Stabilization of proteins by choline-O-sulfate during preparation and NMR measurement2011

    • Author(s)
      Kaori Wakamatsu, Haimei Wang, Masahiko Takahashi, Kazuma Nakazawa, Mitsuhiko Yoshizawa, Tetsuro Demura, Kazuo Hosoda, Shin-ichi Terawaki, Nobukazu Nameki, Kenji Sugase
    • Organizer
      The International Symposium on Nuclear Magnetic Resonance 2011
    • Place of Presentation
      横浜大さん橋ホール
    • Year and Date
      2011-11-17
    • Related Report
      2011 Annual Research Report
  • [Presentation] Stabilization of proteins by cholie-O-sulfate duing preparation and NMR measurement2011

    • Author(s)
      K. Wakamatsu, H. Wang, M. Takahashi, K. Nakazawa, M. Yoshizawa, T. Demura, K. Hosoda, S. Teraw, N. Nameki, K. Sugase
    • Organizer
      The International Symposium on Nuclear Magnetic Resonance 2011
    • Place of Presentation
      横浜大さん橋ホール(神奈川県)
    • Year and Date
      2011-11-15
    • Related Report
      2011 Final Research Report
  • [Presentation] 各種NDSBがタンパク質の凝集防止と安定化に及ぼす効果2011

    • Author(s)
      若松馨, 五十嵐麗樹, 金子敬輔, 高橋雅彦, 真井隆徳, 手塚福栄, 中沢和磨, 高橋玲羅, 王海梅, 石井毅, 細田和男, 寺脇慎一, 行木信一, 窪田健二
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2011-09-22
    • Related Report
      2011 Annual Research Report
  • [Presentation] 各種NDSBがタンパク質の凝集防止と安定化に及ぼす効果2011

    • Author(s)
      若松馨, 五十嵐麗樹, 金子敬輔, 高橋雅彦, 真井隆徳, 手塚福栄, 中沢和磨, 高橋玲羅, 王海梅, 石井毅, 細田和男, 寺脇慎一, 行木信一, 窪田健二
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      国立京都国際会館(京都府)
    • Year and Date
      2011-09-21
    • Related Report
      2011 Final Research Report
  • [Presentation] Elucidation of the mechanisms whereby NDSBs protect proteins from denaturation and aggregation2011

    • Author(s)
      Masahiko Takahashi, Kazuki Igarashi, Keisuke Kaneko, Emi Miura, Haimei Wang, Takeshi Ishii, Kenji Kubota, Kaori Wakamatsu
    • Organizer
      第49回日本生物物理学会年会
    • Place of Presentation
      兵庫県立大学書写キャンパス
    • Year and Date
      2011-09-17
    • Related Report
      2011 Annual Research Report
  • [Presentation] Elucidation of the mechanisms whereby NDSBs protect proteins from denaturation and aggregation2011

    • Author(s)
      M. Takahashi, K. Igarashi, K. Kaneko, E. Miura, H. Wang, T. Ishii, K. Kubota, K. Wakamatsu
    • Organizer
      第49回日本生物物理学会年会
    • Place of Presentation
      兵庫県立大学書写キャンパス(兵庫県)
    • Year and Date
      2011-09-16
    • Related Report
      2011 Final Research Report
  • [Presentation] 蛋白質安定化剤NDSB類が及ぼす種々の効果および蛋白質ハンドリングへの応用2011

    • Author(s)
      若松馨, 五十嵐麗樹, 金子敬輔, 神谷歩, 王海梅, 高橋雅彦, 真井隆徳, 手塚福栄, 中沢和磨, 石井毅, 窪田健二
    • Organizer
      第11回蛋白質科学会年会
    • Place of Presentation
      ホテル阪急エキスポパーク
    • Year and Date
      2011-06-08
    • Related Report
      2011 Annual Research Report
  • [Presentation] NDSB-256がタンパク質の凝集と安定性に及ぼす効果2010

    • Author(s)
      五十嵐麗樹、石井毅、向龍、窪田健二、若松馨
    • Organizer
      第33回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2010-12-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] NDSBによるタンパク質の安定化のメカニズムとその応用2010

    • Author(s)
      金子敬輔、高橋雅彦、三浦絵美、窪田健二、若松馨
    • Organizer
      第33回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2010-12-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] Effects of NDSB, amyloid formation inhibitor, on protein structure2010

    • Author(s)
      Haimei Wang, Mayu Enomoto, Nobukazu Nameki, Kenji Sugase, Kaori Wakamatsu
    • Organizer
      5th International peptide symposium
    • Place of Presentation
      京都国際会館
    • Year and Date
      2010-12-04
    • Related Report
      2010 Annual Research Report
  • [Presentation] Effects of choline-O-sulfate on amyloid formation of hIAPP2010

    • Author(s)
      Mamoru Hagihara, Ayaka Takei, Kaori Wakamatu, Nobukazu Nameki
    • Organizer
      5th International peptide symposium
    • Place of Presentation
      京都国際会館
    • Year and Date
      2010-12-04
    • Related Report
      2010 Annual Research Report
  • [Presentation] NDSBによるGPCRの安定化と抽出効率向上2010

    • Author(s)
      高橋玲羅, 山下直樹, 中島正人, 石井毅, 若松馨
    • Organizer
      日本化学会関東支部群馬地区地域懇談会
    • Place of Presentation
      日本原子力研究開発機構
    • Year and Date
      2010-11-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] 蛋白質・ペプチドの溶液NMRへのスルホベタイン類の応用2010

    • Author(s)
      若松馨, 王海梅, 五十嵐麗樹, 神谷歩, 高橋雅彦, 手塚福栄, 向瓏, 石井毅, 細田和男, 行木信一, 菅瀬謙治
    • Organizer
      第49回NMR討論会
    • Place of Presentation
      タワーホール船堀(東京都)
    • Year and Date
      2010-11-15
    • Related Report
      2011 Final Research Report
  • [Presentation] 蛋白質・ペプチドの溶液NMRへのスルホベタイン類の応用2010

    • Author(s)
      若松馨, 王海梅, 五十嵐麗樹, 神谷歩, 高橋雅彦, 手塚福栄, 向瓏, 石井毅, 細田和男, 行木信一, 菅瀬謙治
    • Organizer
      第49回NMR討論会
    • Place of Presentation
      タワーホール船堀
    • Year and Date
      2010-11-15
    • Related Report
      2010 Annual Research Report
  • [Presentation] バイセルに結合したマガイニン2の構造解析2010

    • Author(s)
      細田和男、向瓏、稲岡斉彦、河野俊之、若松馨
    • Organizer
      第49回NMR討論会
    • Place of Presentation
      タワーホール船堀
    • Year and Date
      2010-11-15
    • Related Report
      2010 Annual Research Report
  • [Presentation] Effects of non-detergent sulfobetaines on protein dynamics2010

    • Author(s)
      Kaori Wakamatau, Haimei Wang, Ayaka Matsui, Nobukazu Nameki, Kenji Sugase
    • Organizer
      第48回日本生物物理学会年会
    • Place of Presentation
      東北大学
    • Year and Date
      2010-09-20
    • Related Report
      2010 Annual Research Report
  • [Presentation] NDSBか類蛋白質の & タイナミクスに及す効果2009

    • Author(s)
      若松馨, 王海梅, 松井文香, 神谷歩, 加藤瀬里, 行木信一, 菅瀬謙治
    • Organizer
      第48回NMR討論会
    • Place of Presentation
      九州大学(福岡県)
    • Year and Date
      2009-11-10
    • Related Report
      2011 Final Research Report
  • [Presentation] NDSB類が蛋白質のダイナミクスに及す効果2009

    • Author(s)
      若松馨, 王海梅, 松井文香, 神谷歩, 加藤瀬里, 行木信一, 菅瀬謙治
    • Organizer
      第48回NMR討論会
    • Place of Presentation
      九州大学
    • Year and Date
      2009-11-10
    • Related Report
      2009 Annual Research Report
  • [Presentation] NDSB類によるタンパク質の安定化:二次構造との相関2009

    • Author(s)
      金子敬輔、五十嵐麗樹、神谷歩、真井隆徳、加藤瀬里、王海梅、石井毅、行木信一、窪田健二、若松馨
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2009-10-21
    • Related Report
      2009 Annual Research Report
  • [Presentation] NDSB類によるタンパク質の安定化2009

    • Author(s)
      金子敬輔、大竹佳樹、窪田健二、若松馨
    • Organizer
      日本生化学会関東支部例会
    • Place of Presentation
      つくば国際会議場
    • Year and Date
      2009-06-20
    • Related Report
      2009 Annual Research Report
  • [Presentation] 蛋白質凝集防止剤のNMRへの応用2009

    • Author(s)
      五十嵐麗樹、神谷歩、向龍、石井毅、若松馨
    • Organizer
      日本生化学会関東支部例会
    • Place of Presentation
      つくば国際会議場
    • Year and Date
      2009-06-20
    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://wakamatsu-lab.dept.eng.gunma-u.ac.jp/Wakamatsu-lab/Tob.html

    • Related Report
      2011 Final Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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