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Study for rapid synthesis and mechanism elucidation of cyclic antifreeze glycopeptide

Research Project

Project/Area Number 23350074
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemistry related to living body
Research InstitutionHokkaido University

Principal Investigator

HINOU HIROSHI  北海道大学, 先端生命科学研究科(研究院), 准教授 (70333333)

Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000)
Fiscal Year 2013: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2012: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2011: ¥12,090,000 (Direct Cost: ¥9,300,000、Indirect Cost: ¥2,790,000)
Keywordsペプチド環化 / 水素結合 / 配座解析 / 単結晶X線回折 / NMR / 糖ペプチド / 不凍活性 / AFGP / 環状ペプチド / 溶媒効果 / pKa / 環化率 / 環化反応 / 不凍糖タンパク質 / 結晶構造 / NMR / 不凍糖ペプチド / 配座
Research Abstract

Cyclic anti-freeze glydopeptide (AFGP) found by our group has different conformation from linear AFGP found from polar fish. To elucidate the structural feature of the cyclic AFGP, we developed novel cyclization method for peptide and glycopeptide by use of hydrogen-bonding property of fluorinated alcohols. Pure cyclic AFGP was obtained by the new method in high yield from solution of corresponding corresponding linear precursor. Interestingly, common cyclization method using DPPA induce C-terminal epimerization. NMR and X-ray crystallographic experiments for cyclic AFGP and corresponding cyclic peptide skeleton revealed anti-parallel beta-sheet structure of the both compound, and glycan modification induce a replacement of amino acid position in the structure.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (48 results)

All 2014 2013 2012 2011 Other

All Journal Article (15 results) (of which Peer Reviewed: 15 results) Presentation (31 results) (of which Invited: 3 results) Remarks (2 results)

  • [Journal Article] A straightforward protocol for the preparation of high performance microarray displaying synthetic MUC1 glycopeptides2014

    • Author(s)
      Takahiko Matsushita, Wataru Takada, Kota Igarashi, Kentaro Naruchi, Fayna Garcia-Martin, Maho Amano, Hiroshi Hinou, Shin-Ichiro Nishimura
    • Journal Title

      BBA-General Subject

      Volume: 59 Issue: 3 Pages: 355-356

    • DOI

      10.1016/j.bbagen.2013.11.009

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of neoglycosphingolipids from methoxyamino-functionalized ceramide2014

    • Author(s)
      Junya Ishida, Hiroshi Hinou, Kentaro Naruchi, Shin-Ichiro Nishimura
    • Journal Title

      Bioorganic Medicianl Chemistry Letters

      Volume: 24 Issue: 4 Pages: 1197-1200

    • DOI

      10.1016/j.bmcl.2013.12.091

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Glycoblotting-based high throughput protocol for the structural characterization of hyaluronan degradation products during enzymatic fragmentation2013

    • Author(s)
      Takayuki Furukawa, Misaki Arai, Fayna G. Martin, Maho Amano, Hiroshi Hinou, Shin-Ichiro Nishimura
    • Journal Title

      Glycoconjugate Journal

      Volume: 30 Issue: 2 Pages: 171-182

    • DOI

      10.1007/s10719-012-9395-0

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Macrocyclic Mechanism-based Inhibitor for Neuraminidases2013

    • Author(s)
      Hirokazu Kai, Hiroshi Hinou, Kentaro Naruchi, Takahiko Matsushita, and Shin-Ichiro Nishimura
    • Journal Title

      Chemistry : A European Journal

      Volume: 19 Issue: 4 Pages: 1364-1372

    • DOI

      10.1002/chem.201200859

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Site-specific conformational alteration induced by sialylation of MUC1 tandem repeating glycopeptides at an epitope region for anti-KL-6 monoclonal antibody2013

    • Author(s)
      Takahiko Matsushita, Naoki Ohyabu, Naoki Fujitani, Kentaro Naruchi, Hiroki Shimizu, Hiroshi Hinou, Shin-Ichiro Nishimura
    • Journal Title

      Biochemistry

      Volume: 52 Issue: 2 Pages: 402-414

    • DOI

      10.1021/bi3013142

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Shin-Ichiro Nishimura "A novel approach for the parallel synthesis of glycopeptides by combining solid-phase peptide synthesis and dendrimer-supported enzymatic modifications2013

    • Author(s)
      Takahiko Matsushita, Seiji Handa, Kentaro Naruchi, Fayna Garcia-Martin, Hiroshi Hinou
    • Journal Title

      Polymer Journal

      Volume: 45 Issue: 8 Pages: 854-862

    • DOI

      10.1038/pj.2013.14

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Microwave-assisted solid-phase synthesis of antifreeze glycopeptides2013

    • Author(s)
      Izumi, R., Matsushita, T., Ohyabu, N., Fujitani, N., Naruchi, K., Shimizu, H., Tsuda, S., Hinou, H., and Nishimura, S.-I
    • Journal Title

      Chem. Eur. J.

      Volume: 19 Issue: 12 Pages: 3913-3920

    • DOI

      10.1002/chem.201203731

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Attomolar-level Detection of Influenza A Virus Hemagglutinin Human H1 and Avian H5 Using Glycan-blotted Field Effect Transistor Biosensor2013

    • Author(s)
      Sho Hideshima, Hiroshi Hinou, Daisuke Ebihara, Ryosuke Sato, Shigeki Kuroiwa, Takuya Nakanishi, Shin-Ichiro Nishimura, Tetsuya Osaka
    • Journal Title

      Analytical Chemistry

      Volume: 85 Issue: 12 Pages: 5641-5644

    • DOI

      10.1021/ac401085c

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A New Approach for the Synthesis of Hyper-Branched N-Glycan Core Structures from Locust Bean Gum2013

    • Author(s)
      H. V. Ravi Kumar, Kentaro Naruchi, Risho Miyoshi, Hiroshi Hinou, Shin-Ichiro Nishimura
    • Journal Title

      Organic Letters

      Volume: 15 Issue: 24 Pages: 6278-6281

    • DOI

      10.1021/ol403140h

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] An efficient protocol for the solid-phase synthesis of glycopeptides under microwave irradiation2012

    • Author(s)
      Fayna Garcia-Martin, Hiroshi Hinou, Takahiko Matsushita, Shun Hayakawa, Shin-Ichiro Nishimura
    • Journal Title

      Organic & Biomolecular Chemistry

      Volume: 10 Pages: 1612-1617

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aglycone-focused randomization of 2-difluoromethylphenylsialoside-type suicide substrates for neuraminidases2012

    • Author(s)
      Hirokazu Kai, Hiroshi Hinou, Shin-Ichiro Nishimura
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 20 Issue: 8 Pages: 2739-2746

    • DOI

      10.1016/j.bmc.2012.02.001

    • Related Report
      2013 Final Research Report 2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Strict stereocontrol by 2, 4-O-di-tert-butylsilylene group on β-glucuronylations2012

    • Author(s)
      Takayuki Furukawa, Hiroshi Hinou, Shin-Ichiro Nishimura
    • Journal Title

      Organic Letters

      Volume: 14 Issue: 8 Pages: 2102-2105

    • DOI

      10.1021/ol300634x

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] H-Bonding Promotion of Peptide Solubility and Cyclization by Fluorinated Alcohol2012

    • Author(s)
      Hiroshi Hinou, Kei Hyugaji, Fayna Garcia-Martin, Shin-Ichiro Nishimura, Fernando Albericio
    • Journal Title

      RSC Advances

      Volume: 2 Issue: 7 Pages: 2729-2731

    • DOI

      10.1039/c2ra01043g

    • Related Report
      2013 Final Research Report 2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Potential Glucuronate Glycosyl Donor with 2-O-acyl-6,3-lactone Structure : Efficient Synthesis of Glycosaminoglycan Disaccharides2011

    • Author(s)
      古川貴之、比能洋、島脇健、西村紳一郎
    • Journal Title

      Tetrahedron Letters

      Volume: 52 Issue: 43 Pages: 5567-5570

    • DOI

      10.1016/j.tetlet.2011.08.024

    • NAID

      120003537883

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Toward Green and Sustainable Chemical Glycosylation : Enhanced Lewis Acidity of Recyclable Solid Super Acid Catalyst, SO_4/ZrO_2 by CaCl_2 Doping2011

    • Author(s)
      比能洋、斉藤尚裕、前田哲宏、神谷裕一、西村紳一郎
    • Journal Title

      Journal of Carbohydrate Chemistry

      Volume: 30 Issue: 7-9 Pages: 575-586

    • DOI

      10.1080/07328303.2011.610545

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] Synthesis and Application of Bicyclic Carbohydrates2014

    • Author(s)
      Hiroshi Hinou
    • Organizer
      International Symposium on Chemical Biology-Drug Discovery
    • Place of Presentation
      Mysore Universitu, Mysore, India
    • Year and Date
      2014-01-10
    • Related Report
      2013 Final Research Report
  • [Presentation] Highly Efficient Synthesis of Hyperbranched N-glycans from Locust Bean Gum2013

    • Author(s)
      H. V. Ravi Kumar, Kentaro Naruchi, Risho Miyoshi, Hiroshi Hinou, Risho Miyoshi, Shin-Ichiro Nishimura
    • Organizer
      246th American Chemical Society Meeting & Exposition
    • Place of Presentation
      Indianapolis (IN), USA
    • Year and Date
      2013-09-08
    • Related Report
      2013 Final Research Report
  • [Presentation] New Strategy for Peptide Cyclization H-bonding effect of fluorinated alcohol2013

    • Author(s)
      Hiroshi Hinou
    • Organizer
      Special Seminar at Chemistry Department of Wane State University
    • Place of Presentation
      Detroit, USA
    • Year and Date
      2013-09-06
    • Related Report
      2013 Final Research Report
  • [Presentation] Modified Mechanism-based Inhibitor for Neuraminidases2013

    • Author(s)
      Hiroshi Hinou, Hirokazu Kai, Shin-Ichiro Nishimura
    • Organizer
      The 11 th International Symposium for Future Drug Discovery & Medical Care
    • Place of Presentation
      Sapporo
    • Year and Date
      2013-08-02
    • Related Report
      2013 Final Research Report
  • [Presentation] Modified Mechanism-based Inhibitor for Neuraminidases2012

    • Author(s)
      Hiroshi Hinou, Hirokazu Kai, Shin-Ichiro Nishimura
    • Organizer
      The 10th International Symposium for Future Drug Discovery & Medical Care
    • Place of Presentation
      Sapporo
    • Year and Date
      2012-10-03
    • Related Report
      2013 Final Research Report
  • [Presentation] 糖誘導体・糖ペプチドの環化と機能制御2012

    • Author(s)
      比能洋
    • Organizer
      日本化学会生体機能関連化学部会第27回若手フォーラム
    • Place of Presentation
      札幌
    • Year and Date
      2012-09-05
    • Related Report
      2013 Final Research Report
  • [Presentation] Solid-Phase Synthesis and Structural Study of Glycopeptide Containing C-Mannosyltriptophan in Human Erythropoietin Receptor2012

    • Author(s)
      Hiroshi Hinou, Yuya abe, and Shin-Ichiro Nishimura
    • Organizer
      International Glycomics Symposium -Increasing the Impact of Glycoscience through New Tools and Technologies-
    • Place of Presentation
      San Sebastian, Spain
    • Year and Date
      2012-07-19
    • Related Report
      2013 Final Research Report
  • [Presentation] ^1C_4配座を有する新奇グルクロン酸糖供与体に関する研究2012

    • Author(s)
      古川貴之、比能洋、西村紳一郎
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      北海道大学(札幌市)
    • Year and Date
      2012-03-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] 糖鎖補足反応を用いた新規糖脂質ライブラリの構築と溶液中における構造解析2012

    • Author(s)
      石田純也、比能洋、西村紳一郎
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      北海道大学(札幌市)
    • Year and Date
      2012-03-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] ムチン型糖ペプチドにおけるTTXモチーフのNMR構造解析2012

    • Author(s)
      早川瞬、松下隆彦、比能洋、西村紳一郎
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      北海道大学(札幌市)
    • Year and Date
      2012-03-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] グライコブロッティング法を用いた異なる種類のヒアルロン酸分解酵素生成ヒアルロン酸断片の同定2012

    • Author(s)
      荒井みさき、古川貴之、ガルシアファイナ、比能洋、天野麻穂、西村紳一郎
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      北海道大学(札幌市)
    • Year and Date
      2012-03-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] 不凍糖ペプチドの効率的環化法の開発と配座解析2012

    • Author(s)
      日向寺慧、比能洋、F.Garcia-Martin、松下隆彦、成地健太郎、西村紳一郎
    • Organizer
      第46回高分子学会北海道支部研究発表会
    • Place of Presentation
      北海道大学(札幌市)
    • Year and Date
      2012-01-31
    • Related Report
      2011 Annual Research Report
  • [Presentation] 機能性デンドリマーを用いた糖ペプチドの酵素化学的合成法2012

    • Author(s)
      半田誠治、松下隆彦、比能洋、西村紳一郎
    • Organizer
      第46回高分子学会北海道支部研究発表会
    • Place of Presentation
      北海道大学(札幌市)
    • Year and Date
      2012-01-31
    • Related Report
      2011 Annual Research Report
  • [Presentation] ヒトエリスロボエチン受容体のC-マンノシルトリプトファン含有当ペプチド領域の合成と配座解析2012

    • Author(s)
      阿部悠弥、比能洋、松下隆彦、Fayna G.Martin、早川瞬、古川貴之、藤谷直樹、成地健太郎、西村紳一郎
    • Organizer
      第46回高分子学会北海道支部研究発表会
    • Place of Presentation
      北海道大学(札幌市)
    • Year and Date
      2012-01-31
    • Related Report
      2011 Annual Research Report
  • [Presentation] H-bonding cyclization of peptide backbone of anti-freeze glycopeptide in fluorinated alcohols2012

    • Author(s)
      Hiroshi Hinou, Kei Hyugaji, Fayna Garcia-Martin, Shin-Ichiro Nishimura, Fernando Albericio
    • Organizer
      XXVI International Carbohydrate Symposium (ICS XXVI)
    • Place of Presentation
      Madrid, Spain
    • Related Report
      2013 Final Research Report
  • [Presentation] Macrocyclic Mechanism-based Inhibitor for Neuraminidases2012

    • Author(s)
      Hiroshi Hinou, Hirokazu Kai, Shin-Ichiro Nishimura
    • Organizer
      XXVI International Carbohydrate Symposium (ICS XXVI)
    • Place of Presentation
      Madrid, Spain
    • Related Report
      2013 Final Research Report
  • [Presentation] H-bonding cyclization of peptide backbone of anti-freeze glycopeptide in fluorinated alcohols2012

    • Author(s)
      Hiroshi Hinou
    • Organizer
      XXVI International Carbohydrate Symposium (ICS XXVI)
    • Place of Presentation
      El Hotel Melia Castilla (Madrid, Spain)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Macrocyclic Mechanism-based Inhibitor for Neuraminidases2012

    • Author(s)
      Hiroshi Hinou
    • Organizer
      XXVI International Carbohydrate Symposium (ICS XXVI)
    • Place of Presentation
      El Hotel Melia Castilla (Madrid, Spain)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Solid-Phase Synthesis and Structural Study of Glycopeptide Containing C-Mannosyltriptophan in Human Erythropoietin Receptor2012

    • Author(s)
      Hiroshi Hinou
    • Organizer
      International Glycomics Symposium -Increasing the Impact of Glycoscience through New Tools and Technologies-
    • Place of Presentation
      Auditorium Tech Park Miramon (San Sebastian, Spain)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Modified Mechanism-based Inhibitor for Neuraminidases2012

    • Author(s)
      Hiroshi Hinou
    • Organizer
      The 10th International Symposium for Future Drug Discovery & Medical Care
    • Place of Presentation
      北海道大学(札幌市)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 糖誘導体・糖ペプチドの環化と機能制御2012

    • Author(s)
      比能 洋
    • Organizer
      日本化学会生体機能関連化学部会第27回若手フォーラム
    • Place of Presentation
      北海道大学(札幌市)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 環状不凍糖タンパク質の効率的合成法の開発2011

    • Author(s)
      日向寺慧、比能洋、F.Garcia-Martin、西村紳一郎
    • Organizer
      2011年度北海道高分子若手研究会
    • Place of Presentation
      洞爺サンパレス(北海道)
    • Year and Date
      2011-08-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] 糖鎖蛍光ナノ微粒子の合成および生きた動物のイメージングへの応用2011

    • Author(s)
      大柳達也、長堀紀子、嶋脇健、比能洋、山下匡、佐々木章、神隆、岩永敏彦、金城政孝、西村紳一郎
    • Organizer
      2011年度北海道高分子若手研究会
    • Place of Presentation
      洞爺サンパレス(北海道)
    • Year and Date
      2011-08-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] 配座反転糖供与体を利用したグリコサミノグリカン二糖の合成研究2011

    • Author(s)
      古川貴之、比能洋、西村紳一郎
    • Organizer
      2011年度北海道高分子若手研究会
    • Place of Presentation
      洞爺サンパレス(北海道)
    • Year and Date
      2011-08-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] 糖鎖補足反応を用いた新規糖脂質ライブラリの構築と溶液中における構造解析2011

    • Author(s)
      石田純也、比能洋、西村紳一郎
    • Organizer
      2011年度北海道高分子若手研究会
    • Place of Presentation
      洞爺サンパレス(北海道)
    • Year and Date
      2011-08-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] ヒトErythropoietin Receptor由来C-マンノシルトリプトファン含有糖ペプチドの合成および構造解析2011

    • Author(s)
      阿部悠弥、比能洋、成地健太郎、西村紳一郎
    • Organizer
      2011年度北海道高分子若手研究会
    • Place of Presentation
      洞爺サンパレス(北海道)
    • Year and Date
      2011-08-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] 機能性デンドリマーを用いた糖ペプチドの酵素化学的合成法2011

    • Author(s)
      半田誠治、松下隆彦、比能洋、西村紳一郎
    • Organizer
      2011年度北海道高分子若手研究会
    • Place of Presentation
      洞爺サンパレス(北海道)
    • Year and Date
      2011-08-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] ケイ素保護基を利用した糖ペプチドの迅速固相合成法2011

    • Author(s)
      藤井宏圭、松下隆彦、比能洋、西村紳一郎
    • Organizer
      2011年度北海道高分子若手研究会
    • Place of Presentation
      洞爺サンパレス(北海道)
    • Year and Date
      2011-08-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] New Strategy for Peptide Cyclization H-bonding effect of fluorinated alcohol

    • Author(s)
      Hiroshi Hinou
    • Organizer
      Special Seminar at Chemistry Department of Wane State University
    • Place of Presentation
      Wayne State University (USA)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Synthesis and Application of Bicyclic Carbohydrates

    • Author(s)
      Hiroshi Hinou
    • Organizer
      International Symposium on Chemical Biology-Drug Discovery
    • Place of Presentation
      Mysore University (India)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Highly Efficient Synthesis of Hyperbranched N-glycans from Locust Bean Gum

    • Author(s)
      H. V. Ravi Kumar, Kentaro Naruchi, Risho Miyoshi, Hiroshi Hinou, Risho Miyoshi, Shin-Ichiro Nishimura
    • Organizer
      246th American Chemical Society Meeting & Exposition
    • Place of Presentation
      Indianapolis Conference Center (USA)
    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

      http://altair.sci.hokudai.ac.jp/g4/

    • Related Report
      2013 Final Research Report
  • [Remarks] publication list

    • URL

      http://altair.sci.hokudai.ac.jp/g4/publications.html

    • Related Report
      2012 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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