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2009 Fiscal Year Final Research Report

Comprehensive Studies toward Synthesis of Glycoproteins

Research Project

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Project/Area Number 17GS0420
Research Category

Grant-in-Aid for Creative Scientific Research

Allocation TypeSingle-year Grants
Research InstitutionThe Institute of Physical and Chemical Research

Principal Investigator

ITO Yukishige  The Institute of Physical and Chemical Research, 基幹研究所・細胞制御化学研究室, 主任研究員 (80168385)

Co-Investigator(Kenkyū-buntansha) NAKAHARA Yoshiaki  東海大学, 工学部・生命化学科, 教授 (50087574)
KAJIHARA Yasuhiro  大阪大学, 大学院・理学研究科・化学専攻, 教授 (50275020)
Project Period (FY) 2005 – 2009
Keywords糖タンパク質 / 糖鎖 / 細胞内プロセシング / 化学合成 / チオエステル法 / エリスロポエチン
Research Abstract

・Analysis of intracellular glycoprotein processing was conducted by using synthetic high-mannose-type glycans and their derivatives.
・Thioester forming reaction and amino-protecting group were developed and applied to syntheses of glycoproteins and dendrimers. A novel efficient reaction which utilize an ultra-high pressure was developed.
・Syntheses of glycoproteins which carry complex-type glycans were achieved. The most significant among them is the synthesis of erythmpoietin (EPO), a medically important glycoprotein. In vitro assay clarified that its cell-proliferating activity was almost indistinguishable with native EPO.

  • Research Products

    (44 results)

All 2010 2009 2008 2007 2006 2005 Other

All Journal Article (30 results) Remarks (6 results) Patent(Industrial Property Rights) (8 results)

  • [Journal Article] The Mercaptomethyl Group Facilitates an Efficient One-Pot Ligation at Xaa-Ser/Thr for (Glyco) peptide Synthesis2010

    • Author(s)
      Hojo H. Ozawa C., Katayama H., Ueki A., Nakahara Y. Nakahara Y.
    • Journal Title

      Angew.Chem.Int.Ed. 49

      Pages: 5318-5321

  • [Journal Article] Correct Disulfide Pairing Is Required for the Biological Activity of Crustacean Androgenic Gland Hormone (AGH) : Synthetic Studies of AGH2010

    • Author(s)
      Katayama H., Hojo H., Ohira T., Ishii A., Nozaki T., Goto K., Nakahara Y., Takahashi T., Hasegawa Y., Nagasawa H., Nakahara Y.
    • Journal Title

      Biochemistry 49

      Pages: 1798-1807

  • [Journal Article] High-pressure-promoted Fmoc-aminoacylation of N-ethylcysteine : Preparation of key devices for the solid-phase synthesis of peptide thioesters2010

    • Author(s)
      Nakahara Y., Matsuo I., Ito Y., Ubagai R., Hojo, H., Nakahara Y.
    • Journal Title

      Tetrahedron Lett 51

      Pages: 407-410

  • [Journal Article] Genetic analysis of glucosidase II β-subunit in trimming of high-mannose-type glycans2009

    • Author(s)
      Watanabe T., Totani K., Matsuo I., Maruyama J., Kitamoto K., Ito Y.
    • Journal Title

      Glycobiology 19

      Pages: 834-840

  • [Journal Article] Synthesis of undecaprenyl pyrophosphate-linked glycans as donor substrates for bacterial protein N-glycosylation2009

    • Author(s)
      Lee Y.-J., Ishiwata A., Ito Y.
    • Journal Title

      Tetrahedron 65

      Pages: 6310-6319

  • [Journal Article] Design and Synthesis of Homogeneous Erythropoietin Analogue with Two Human Complex-Type Sialyloligosaccharides2009

    • Author(s)
      Hirano K., Macmillan D., Tezuka K., Tsuji T., Kajihara Y.
    • Journal Title

      Angew.Chem.Int.Ed. 48

      Pages: 9557-9560

  • [Journal Article] NAP Ether-mediated intramolecular aglycon delivery : a unified strategy for 1, 2-cis glycosylation2008

    • Author(s)
      Ishiwata A., Munemura Y., Ito Y.
    • Journal Title

      Eur.J.Org.Chem. 25

      Pages: 4250-4263

  • [Journal Article] Stereoselective synthesis of β-L-Rhamnopyranoside2008

    • Author(s)
      Lee Y.J., Ishiwata A., Ito Y.
    • Journal Title

      J.Am.Chem.Soc. 130(20)

      Pages: 6330-6331

  • [Journal Article] Effects of Macromolecular crowding on glycoprotein processing enzymes2008

    • Author(s)
      Totani K., Ihara Y., Matsuo I., Ito Y.
    • Journal Title

      J.Am.Chem.Soc. 130

      Pages: 2101-2107

  • [Journal Article] Application of a novel thioesterification reaction to the synthesis of chemokine CCL27 by the modified thioester method.2008

    • Author(s)
      Hojo H, Murasawa Y., Katayama H., Ohira T., Nakahara, Y., Nakahara, Y.
    • Journal Title

      Org.Biomol.Chem. 6

      Pages: 1808-1813

  • [Journal Article] Efficient sequential segment coupling using N-alkylcystein-assisted thioesterification for glycopeptides dendrimer synthesis2008

    • Author(s)
      Ozawa C., Katayama H., Hojo H., Nakahara Y., Nakahara Y.
    • Journal Title

      Org.Lett. 10

      Pages: 3531-3533

  • [Journal Article] Chemical synthesis of a glycoprotein having an intact human complex-type sialyloligosaccharide under the Boc and Fmoc synthetic strategies2008

    • Author(s)
      Yamamoto N., Tanabe Y., Okamoto R., Dawson P.E., Kaiihara Y.
    • Journal Title

      J.Am.Chem.Soc. 130

      Pages: 501-510

  • [Journal Article] Analysis of ER-associated glycoprotein degradation using synthetic glycopeptide probes2007

    • Author(s)
      Hagihara S., Goda K., Matsuo I., Ito Y.
    • Journal Title

      Biochem.Biophys.Res.Commun. 360

      Pages: 357-362

  • [Journal Article] Synthesis of N-linked glycan derived from Gram-negative bacterium, Campylobacter jejuni2007

    • Author(s)
      Amin M.N., Ishiwata A., Ito Y.
    • Journal Title

      Tetrahedron 63

      Pages: 8181-8198

  • [Journal Article] Synthesis of a natural oligosaccharide antibiotic active against Helicobacter pylori2007

    • Author(s)
      Manabe S., Ishii K., Ito Y.
    • Journal Title

      J.Org.Chem. 72

      Pages: 6107-6115

  • [Journal Article] Fluorescently labeled inhibitor for profiling cytoplasmic peptide : N-glycanase2007

    • Author(s)
      Hagihara S., Miyazaki A., Matsuo I., Tatami A., Suzuki T., Ito Y.
    • Journal Title

      Glycobiology 17

      Pages: 1070-1076

  • [Journal Article] An approach for a synthesis of asparagine-linked sialylglycopeptides having intact and homogeneous complex-type undecadisialyloligosaccharides2007

    • Author(s)
      Yamamoto N., Takayanagi A., Yoshino A., Sakakibara T., Kajihara Y.
    • Journal Title

      Chem.Eur.J. 13

      Pages: 613-625

  • [Journal Article] Synthesis of biantennary LacNAc-linked O-glycan (core 4) and glycopeptide thioester by benzyl protection strategy : Rapid zinc reduction of G1cNTCA to GIcNAc by microwave irradiation2007

    • Author(s)
      Ueki A., Nakahara Y., Hojo H., Nakahara Y.
    • Journal Title

      Tetrahedron 63

      Pages: 2170-2181

  • [Journal Article] N-Alkyl cystein-assisted thioesterification of peptides2007

    • Author(s)
      Hojo H., Onuma Y., Akimoto Y., Nakahara Y., Nakahara Y.
    • Journal Title

      Tetrahedron Lett. 48

      Pages: 25-28

  • [Journal Article] An approach for a synthesis of asparagine-linked sialylglycopeptides having intact and homogeneous complex-type undecadisialyloligosaccharides2007

    • Author(s)
      Yamamoto N., Takayanagi A., Yoshino A., Sakakibara T., Kajihara Y.
    • Journal Title

      Chem.Eur.J. 13(2)

      Pages: 613-625

  • [Journal Article] Convenient synthesis of a sialylglycopeptide-thioester having an intact and homogeneous complex-type disialyl-oligosaccharide2006

    • Author(s)
      Kajihara Y Yoshihara A., Hirano K., Yamamoto N.
    • Journal Title

      Carbohydr.Res. 341(10)

      Pages: 1333-1340

  • [Journal Article] Highly efficient synthesis of sialylglycopeptides overcoming unexpected aspartimide formation during activation of Fmoc-Asn (sundecadisialyloligosaccharide)-OH2006

    • Author(s)
      Yamamoto P.E., Kajihara. Y.
    • Journal Title

      Tetrahedron Lett. 47(8)

      Pages: 1341-1346

  • [Journal Article] Substrate specificity analysis of endoplasmic reticulum glucosidase II using synthetic high mannose-type glycans2006

    • Author(s)
      Totani K., Ihara Y., Matsuo I., Ito Y.
    • Journal Title

      J.Biol.Chem. 281

      Pages: 31502-31508

  • [Journal Article] Comprehensive synthesis of ER related high-mannose-type sugar chains by covergent strategy2006

    • Author(s)
      Matsuo I., Totani K., Tatami A., Ito Y.
    • Journal Title

      Tetrahedron 62

      Pages: 8262-8277

  • [Journal Article] Facile synthesis of oligosaccharide probes for the analysis of protein-carbohydrate interactions2006

    • Author(s)
      Takatani M., Ito Y.
    • Journal Title

      Chem.Asian J. 1

      Pages: 64-75

  • [Journal Article] Design and synthesis of oligosaccharides that interfere with glycoprotein quality-control systems2005

    • Author(s)
      Arai M.A., Matsuo I., Hagihara S., Totani K., Maruyama J.-i., Kitamoto K., Ito Y.
    • Journal Title

      Chem Bio Chem. 6

      Pages: 2281-2289

  • [Journal Article] Synthetic substrates for an endoplasmic reticulum protein-folding sensor, UDP-glucose : Glycoprotein glucosyltransferase2005

    • Author(s)
      Totani K., Ihara Y., Matsuo I., Koshino H., Ito Y.
    • Journal Title

      Angew.Chem.Int.Ed. 44

      Pages: 7950-7954

  • [Journal Article] First chemical synthesis of triglucosylated tetradecasaccharide (Glc3Man9GlcNAc2), a common precursor of asparagine-linked oligosaccharides2005

    • Author(s)
      Matsuo I., Kashiwagi T., Totani K., Ito Y.
    • Journal Title

      Tetrahedron Lett. 46

      Pages: 4197-4200

  • [Journal Article] Thermodynamic analysis of interactions between N-linked sugar chains and F-box protein Fbsl2005

    • Author(s)
      Hagihara S., Totani K., Matsuo I., Ito Y.
    • Journal Title

      J.Med.Chem. 48

      Pages: 3126-3129

  • [Journal Article] Chemical Synthesis of 23 kDa Glycoprotein by Repetitive Segment Condensation : A Synthesis of MUC2 Basal Motif Carrying Multiple O-GalNAc Moieties2005

    • Author(s)
      Hojo H., Matsumoto Y., Nakahara Y., Ito E., Suzuki Y., Suzuki M., Suzuki A., Nakahara Y.
    • Journal Title

      J.Am.Chem.Soc. 127

      Pages: 13720-13725

  • [Remarks] 2009年7月第24回国際糖質学会で国際賞であるThe Roy L.Whistler Intemational Award in Carbohydrate Chemistryを伊藤幸成が受賞した.

  • [Remarks] Angewndte.Chem.Int.Ed., 2009, 49, 9557-9560に掲載されたエリスロポイエチンの合成に関する論文(論文8)はin side coverに採用された.その成果は、平成21年10月12日の日本経済新聞の科学面で紹介された.

  • [Remarks] J.Am.Chem.Soc., 2008, 130, 501-510に掲載された糖タンパク質の化学合成(論文12)は、12月8日の日本経済新聞社会面、12月12日朝日新聞科学面で、また12月8日のNHK「おはよう日本」で紹介された.

  • [Remarks] Eur.J.Org.Chem., 2008, 25, 4250-4263に掲載された高選択的グリコシル化反応に関す論文(論文7)は表紙に採用された.

  • [Remarks] J.Biol.Chem., 2006, 281, 31502-31508に掲載されたGlucosidase IIの特異性解析(論文23)は表紙に採用された.

  • [Remarks] Tetrahedron Lett., 2005, 46, 4197-4200に掲載された14糖の合成研究(論文28)は表紙に採用された.

  • [Patent(Industrial Property Rights)] 糖鎖付加AILIM細胞外ドメイン及びその製造方法2009

    • Inventor(s)
      梶原康宏, 辻孝, 他
    • Industrial Property Number
      特願2009-16809
    • Filing Date
      2009-07-16
  • [Patent(Industrial Property Rights)] ペプチドの製造方法2009

    • Inventor(s)
      北條裕信, 中原義昭
    • Industrial Property Number
      学校法人東海大学国際PCT/JP2009/005180
    • Filing Date
      2009-06-10
  • [Patent(Industrial Property Rights)] 均一な糖鎖構造を有するエリスロポエチン誘導体2008

    • Inventor(s)
      梶原康宏, デレク・マクミラン, 平野桐子, 他
    • Industrial Property Number
      国際出願番号2008-209583
    • Filing Date
      2008-08-18
  • [Patent(Industrial Property Rights)] 糖鎖ライブラリの作成方法及びその利用2007

    • Inventor(s)
      松尾一郎, 伊藤幸成
    • Industrial Property Number
      国際出願番号2006-124468
    • Filing Date
      2007-07-23
  • [Patent(Industrial Property Rights)] ペプチドのチオエステル化合物の製造方法2007

    • Inventor(s)
      梶原康宏, 山本直樹, 他
    • Industrial Property Number
      国際出願番号2008-508707
    • Filing Date
      2007-03-28
  • [Patent(Industrial Property Rights)] ペプチドチオエステルの製造方法2006

    • Inventor(s)
      北條裕信, 中原義昭
    • Industrial Property Number
      特願2006-275022
    • Filing Date
      2006-10-06
  • [Patent(Industrial Property Rights)] コア4型構造を有するO-結合型糖タンパク質関連化合物およびその製造方法2006

    • Inventor(s)
      中原義昭, 北條裕信, 植木章晴
    • Industrial Property Number
      特願2006-200069
    • Filing Date
      2006-07-21
  • [Patent(Industrial Property Rights)] 糖鎖ライブラリの作成方法及びその利用2006

    • Inventor(s)
      松尾一郎, 伊藤幸成
    • Industrial Property Number
      国内出願番号2006-124468
    • Filing Date
      2006-04-27

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Published: 2012-01-26   Modified: 2016-04-21  

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