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Synthetic study of the O-glycoprotein using the solubilizing method

Research Project

Project/Area Number 15K21124
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Bio-related chemistry
Biomolecular chemistry
Research InstitutionOsaka University

Principal Investigator

Asahina Yuya  大阪大学, たんぱく質研究所, 助教 (10737232)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords糖ペプチド / 糖タンパク質 / 極性反転 / 可溶化 / ペプチドライゲーション / 4-ピコリル基(Pic) / インターロイキン-2 / シアル酸 / チオエステル法 / 親水性保護基 / 極性反転保護 / O-結合型糖鎖 / N-アルキルシステイン
Outline of Final Research Achievements

In this study, we successfully established a novel solubilizing method using 4-picolyl (Pic) group, which realized the synthesis of the glycoprotein, human interleukin-2 (IL-2), containing C-terminal poor solubility regions. Pic ester was introduced to the carboxy group of Glu residues of the C-terminal region, effectively solubilizing the poor solubility peptide. In the next step, the peptide ligation using the one-pot thioester method was performed to obtain the entire polypeptide. After the polypeptide was lead to the final product via deprotection and folding, the synthetic one was investigated by CD analysis and T-cell proliferation assay, which indicated the success of the chemical synthesis of IL-2 having homogeneous sugar chain.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (20 results)

All 2017 2016 2015 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Acknowledgement Compliant: 1 results) Presentation (10 results) (of which Int'l Joint Research: 1 results) Remarks (2 results)

  • [Journal Article] One-pot native chemical ligation by combination of two orthogonal thioester precursors2017

    • Author(s)
      Y. Asahina, Toru Kawakami and Hironobu Hojo
    • Journal Title

      Chem. Commun

      Volume: 53 Issue: 13 Pages: 2114-2117

    • DOI

      10.1039/c6cc10243c

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of the One-pot Ligation by Using Two Orthogonal Thioesterification Devices2017

    • Author(s)
      Yuya Asahina, Toru Kawakami, Hironobu Hojo
    • Journal Title

      Peptide Science (Proceeding)

      Volume: -

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of Interleukin-2 Having Core 1 Type Disaccharide by the Reverse Polarity Protection Strategy2016

    • Author(s)
      Rina Fujimoto, Yuya Asahina, Shinobu Komiya, Ami Ohagi, Hiroko Tamagaki, Katsuhiro Nakagawa, Takashi Sato, Shizuo Akira, Toshifumi Takao, Akira Ishii, Yohsiaki Nakahara, Hironobu, Hojo
    • Journal Title

      Peptide Science 2015: H. Hojo, T. Inazu, H. Katayama (Eds.)

      Volume: - Pages: 119-122

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synthesis of O-Linked Glycopeptide Thioester by the 4-Methylbenzyl Protection Strategy2016

    • Author(s)
      Naoki Takeda, Yuya Asahina, Rina Fujimoto, Akemi Suzuki, Hironobu Hojo
    • Journal Title

      Peptide Science 2015: H. Hojo, T. Inazu, H. Katayama (Eds.)

      Volume: - Pages: 123-124

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Study on a Preparation of Prolyl Thioester by the N-Alkylcysteine Method2016

    • Author(s)
      Ami Ohagi, Yuya Asahina, Hironobu Hojo
    • Journal Title

      Peptide Science 2015: H. Hojo, T. Inazu, H. Katayama (Eds.)

      Volume: - Pages: 135-136

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Chemical Synthesis of O-Glycosylated Human Interleukin-2 by the Reverse Polarity Protection Strategy2015

    • Author(s)
      Yuya Asahina, Shinobu Komiya, Ami Ohagi, Rina Fujimoto,Hiroko Tamagaki, Katsuhiro Nakagawa, Takashi Sato,Shizuo Akira, Toshifumi Takao,Akira Ishii, Yoshiaki Nakahara, Hironobu Hojo
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 54 Issue: 28 Pages: 8226-8230

    • DOI

      10.1002/anie.201501847

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Chemoenzymatic Synthesis of Glycoprotein Using the Peptide Ligation Chemistry2015

    • Author(s)
      Yuya Asahina
    • Journal Title

      Trends in Glycoscience and Glycotechnology

      Volume: 27 Issue: 157 Pages: E15-E19

    • DOI

      10.4052/tigg.1414.4E

    • NAID

      130005099230

    • ISSN
      0915-7352, 1883-2113
    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Chemoenzymatic Synthesis of Glycoprotein Using the Peptide Ligation Chemistry (Jpn. Ed.)2015

    • Author(s)
      朝比奈 雄也
    • Journal Title

      Trends in Glycoscience and Glycotechnology

      Volume: 27 Issue: 157 Pages: J15-J20

    • DOI

      10.4052/tigg.1414.4J

    • NAID

      130005099227

    • ISSN
      0915-7352, 1883-2113
    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] 直交型チオエステル化素子を利用した ヒトヒストンH4の化学合成2017

    • Author(s)
      朝比奈雄也、川上徹、北條裕信
    • Organizer
      日本農芸化学会2017年会
    • Place of Presentation
      京都女子大学(京都府、京都市)
    • Year and Date
      2017-03-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] カベオリン-1の化学合成研究及び細胞膜内ドメインの構造解析2017

    • Author(s)
      藤本梨菜、武居俊樹、朝比奈雄也、佐藤毅、北條裕信
    • Organizer
      日本農芸化学会2017年会
    • Place of Presentation
      京都女子大学(京都府、京都市)
    • Year and Date
      2017-03-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] TFA感受性保護基を用いたシアリル糖ペプチドの合成2017

    • Author(s)
      竹田直樹、武居俊樹、朝比奈雄也、北條裕信
    • Organizer
      日本農芸化学会2017年会
    • Place of Presentation
      京都女子大学(京都府、京都市)
    • Year and Date
      2017-03-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] STUDY FOR DEVELOPMENT OF THE ONE-POT LIGATION BY USING TWO ORTHOGONAL THIOESTERIFICATION DEVICES2016

    • Author(s)
      Yuya Asahina, Toru Kawakami, Hironobu Hojo
    • Organizer
      第53回ペプチド討論会
    • Place of Presentation
      京都テルサ(京都府、京都市)
    • Year and Date
      2016-10-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] Total Synthesis of Human Interleukin-2 Having Core 1 Disaccharide by the Reverse Polarity Protection Strategy2016

    • Author(s)
      Yuya Asahina, Shinobu Komiya, Ami Ohagi, Rina Fujimoto, Hiroko Tamagaki, Katsuhiro Nakagawa, Takashi Sato, Shizuo Akira, Toshifumi Takao, Akira Ishii, Yoshiaki Nakahara, Hironobu Hojo
    • Organizer
      8th International Peptide Symposium
    • Place of Presentation
      ライプツィヒ大学(ライプツィヒ、ドイツ)
    • Year and Date
      2016-09-04
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 4-メチルベンジル基を用いたalpha-シアリル糖ペプチドの合成研究2016

    • Author(s)
      竹田直樹、武居俊樹、朝比奈雄也、北條裕信
    • Organizer
      第35回日本糖質学会年会
    • Place of Presentation
      高知市文化プラザ かるぽーと(高知県高知市)
    • Year and Date
      2016-09-01
    • Related Report
      2016 Annual Research Report
  • [Presentation] STUDY ON A PREPARATION OF PROLYL THIOESTER BY THE N- ALKYLCYSTEINE METHOD2015

    • Author(s)
      Ami Ohagi, Yuya Asahina, Hironobu Hojo
    • Organizer
      第52回日本ペプチド討論会
    • Place of Presentation
      平塚公民館( 神奈川県平塚市 )
    • Year and Date
      2015-11-16
    • Related Report
      2015 Research-status Report
  • [Presentation] TOTAL SYNTHESIS OF INTERLEUKIN-2 HAVING CORE 1 TYPE DISACCHARIDE BY THE REVERSE POLARITY PROTECTION STRATEGY2015

    • Author(s)
      Rina Fujimoto, Yuya Asahina, Shinobu Komiya, Ami Ohagi, Hiroko Tamagaki, Katsuhiro Nakagawa, Takashi Sato, Shizuo Akira, Toshifumi Takao, Akira Ishii, Yoshiaki Nakahara, Hironobu Hojo
    • Organizer
      第52回日本ペプチド討論会
    • Place of Presentation
      平塚公民館( 神奈川県平塚市 )
    • Year and Date
      2015-11-16
    • Related Report
      2015 Research-status Report
  • [Presentation] SYNTHESIS OF O-LINKED GLYCOPEPTIDE THIOESTER BY THE 4- METHYLBENZYL PROTECTION STRATEGY2015

    • Author(s)
      Naoki Takeda, Yuya Asahina, Rina Fujimoto, Akemi Suzuki, Hironobu Hojo
    • Organizer
      第52回日本ペプチド討論会
    • Place of Presentation
      平塚公民館( 神奈川県平塚市 )
    • Year and Date
      2015-11-16
    • Related Report
      2015 Research-status Report
  • [Presentation] O-結合型糖鎖を有するインターロイキン-2の化学合成2015

    • Author(s)
      朝比奈雄也、小宮忍、大萩亜美、藤本梨菜、玉垣裕子、中川勝博、佐藤荘、審良静男、石井彰、高尾敏文、中原義昭、北條裕信
    • Organizer
      第34回日本糖質学会年会
    • Place of Presentation
      東京大学安田講堂( 東京都文京区 )
    • Year and Date
      2015-07-31
    • Related Report
      2015 Research-status Report
  • [Remarks] 2種類のチオエステル化前駆体を利用したワンポットNCL法

    • URL

      http://www.protein.osaka-u.ac.jp/organic/res_desc/index.html#cpenac

    • Related Report
      2016 Annual Research Report
  • [Remarks] IL2の化学合成

    • URL

      http://www.protein.osaka-u.ac.jp/organic/res_desc/index.html#IL2

    • Related Report
      2016 Annual Research Report

URL: 

Published: 2015-04-16   Modified: 2018-03-22  

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