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2011 Fiscal Year Final Research Report

Development of methodologies for catalytic decomposition of proteins

Research Project

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Project/Area Number 21390031
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Drug development chemistry
Research InstitutionThe University of Tokushima

Principal Investigator

OTAKA Akira  徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (20201973)

Co-Investigator(Kenkyū-buntansha) SHIGENAGA Akira  徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (10423394)
Project Period (FY) 2009 – 2011
Keywordsペプチド / ペプチドミメティック / 外部刺激応答型アミノ酸 / ペプチド結合切断 / 標的タンパク質 / ホスファターゼ抵抗性リン酸化アミノ酸
Research Abstract

Analysis of protein functions has been indispensable for disclose of unknown cellar phenomena and drug development. Our purpose in this research is the development of methodologies for catalytic decomposition of proteins, which leads to the uncovering protein functions. We have developed a wide variety of chemical devise for elucidation of peptides-and proteins-associated events, including stimulus-responsive amino acids, peptide mimetics, and nonhydrolyzable phosphoamino acids. On the basis of these researches, we have developed several chemical means for the catalytic protein decomposition.

  • Research Products

    (35 results)

All 2012 2011 2010 2009 Other

All Journal Article (30 results) (of which Peer Reviewed: 30 results) Presentation (2 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Development of a reduction-responsive amino acid that induces peptide bond cleavage in hypoxic cells2012

    • Author(s)
      Shigenaga, A.; Ogura, K.; Hirakawa, H.; Yamamoto, J.; Ebisuno, K.; Miyamoto, L.; Ishizawa, K.; Tsuchiya, K.; Otaka, A
    • Journal Title

      ChemBioChem

      Volume: 13 Pages: 968-971

    • DOI

      doi:10.1002/cbic.201200141

    • Peer Reviewed
  • [Journal Article] Caged ceramide which releases parent ceramide after UV-induced amide bond cleavage followed by intramolecular O-N acyl transfer2012

    • Author(s)
      Shigenaga, A.; Hirakawa, H.; Yamamoto, J.; Ogura, K.; Denda, M.; Yamaguchi, K.; Otaka, A
    • Journal Title

      Peptide Science 2011

      Pages: 385-386

    • Peer Reviewed
  • [Journal Article] Double-kinetically controlled proline ligation2012

    • Author(s)
      Ding, H.; Sato, K.; Morishita, K.; Shigenaga, A.; Otaka, A
    • Journal Title

      Peptide Science 2011

      Pages: 133-134

    • Peer Reviewed
  • [Journal Article] N-Sulfanyl-ethylanilide peptide : a peptide thioester equivalent which can directly participate in native chemical ligation2012

    • Author(s)
      Sato, K.; Tsuda, S.; Sakamoto, K.; Shigenaga, A.; Otaka, A
    • Journal Title

      Peptide Science 2011

      Pages: 13-14

    • Peer Reviewed
  • [Journal Article] Development of UV-responsive catch-and-release system of a cysteine protease model peptide2011

    • Author(s)
      Shigenaga, A.; Morishita, K.; Yamaguchi, K.; Ding, H.; Ebisuno, K.; Sato, K.; Yamamoto, J.; Akaji, K.; Otaka, A
    • Journal Title

      Tetrahedron

      Volume: 67 Pages: 8879-8886

    • DOI

      doi:10.1016/j.tet.2011.09.062

    • Peer Reviewed
  • [Journal Article] Design and synthesis of caged ceramide : UV-responsive ceramide releasing system based on UV-induced amide bond cleavage followed by O-N acyl transfer2011

    • Author(s)
      Shigenaga, A.; Hirakawa, H.; Yamamoto, J.; Ogura, K.; Denda, M.; Yamaguchi, K.; Tsuji, D.; Itoh, K.; Otaka, A
    • Journal Title

      Tetrahedron

      Volume: 67 Pages: 3984-3990

    • DOI

      doi:10.1016/j.tet.2011.04.048

    • Peer Reviewed
  • [Journal Article] Dual kinetically-controlled native chemical ligation using a combi-nation of sulfanylproline and sulfanyl-ethylanilide peptide2011

    • Author(s)
      Ding, H.; Shigenaga, A.; Sato, K.; Morishita, K.; Otaka, A
    • Journal Title

      Org. Lett

      Volume: 13 Pages: 5588-5591

    • DOI

      doi:10.1021/ol202316v

    • Peer Reviewed
  • [Journal Article] N-Sulfanylethylanilide peptide as a crypto-thioester peptide2011

    • Author(s)
      Sato, K.; Shigenaga, A.; Tsuji, K.; Tsuda, S.; Sumikawa, Y.; Sakamoto, K.; Otaka, A
    • Journal Title

      ChemBioChem

      Volume: 12 Pages: 1840-1844

    • DOI

      doi:10.1002/cbic.201100241

    • Peer Reviewed
  • [Journal Article] Application of N-C-or C-N-directed sequential native chemical ligation to the preparation of CXCL14 analogs and their biological evaluation2011

    • Author(s)
      Tsuji, K.; Shigenaga, A.; Sumikawa, Y.; Tanegashima, K.; Sato, K.; Aihara, K.; Hara, T.; Otaka, A
    • Journal Title

      Bioorg. Med. Chem

      Volume: 19 Pages: 4014-4020

    • DOI

      doi:10.1016/j.bmc.2011.05.018

    • Peer Reviewed
  • [Journal Article] N-Sulfanylethyl-anilide derivative as a peptide thioester equivalent2011

    • Author(s)
      Sato, K.; Tsuda, S.; Tsuji, K.; Sakamoto, K.; Shigenaga, A.; Otaka, A
    • Journal Title

      Proceedings of the Twenty-Second American Peptide Symposium

      Pages: 72-73

    • Peer Reviewed
  • [Journal Article] Synthesis of CXCL14 and its derivatives utilizing C to N or N to C directive sequential NCL protocol2011

    • Author(s)
      Tsuji, K.; Sumikawa, Y.; Tanegashima, K.; Shigenaga, A.; Hara, T.; Otaka, A
    • Journal Title

      Proceedings of the Twenty-Second American Peptide Symposium

      Pages: 74-75

    • Peer Reviewed
  • [Journal Article] Development of amide bond cleavage device with application to chemical biology use2011

    • Author(s)
      Otaka, A.; Shigenaga, A
    • Journal Title

      Peptide Science 2010

      Pages: 49

    • Peer Reviewed
  • [Journal Article] Synthesis and biological evaluation of CXCL14 and its derivatives2011

    • Author(s)
      Tsuji, K.; Sumikawa, Y.; Tanegashima, K.; Shigenaga, A.; Hara, T.; Otaka, A
    • Journal Title

      Peptide Science 2010

      Pages: 182

    • Peer Reviewed
  • [Journal Article] Enantioselective synthesis of stimulus-responsive amino acid via pyrrolidinyl tetrazole catalyzed asymmetricα-amination of aldehyde2011

    • Author(s)
      Shigenaga, A.; Yamamoto, J.; Nishioka, N.; Denda, M.; Otaka, A
    • Journal Title

      Peptide Science 2010

      Pages: 202

    • Peer Reviewed
  • [Journal Article] Native chemical ligation using N-peptidyl anilide as crypto-thioester2011

    • Author(s)
      Sato, K.; Tsuda, S.; Maeda, N.; Denda, M.; Shigenaga, A.; Otaka, A
    • Journal Title

      Peptide Science 2010

      Pages: 203

    • Peer Reviewed
  • [Journal Article] Synthesis of nonhydrolyzable AMPylated amino acid analogues for uncovering the physiological role of AMPylation2011

    • Author(s)
      Ogura, K.; Hirakawa, H.; Shigenaga, A.; Otaka, A
    • Journal Title

      Peptide Science 2010

      Pages: 205

    • Peer Reviewed
  • [Journal Article] Development of recapturable cleavable linker for efficient enrichment and specific labeling of target proteins2011

    • Author(s)
      Yamamoto, J.; Maeda, N.; Denda, M.; Shigenaga, A.; Otaka, A
    • Journal Title

      Peptide Science 2010

      Pages: 232

    • Peer Reviewed
  • [Journal Article] Development of stimulus responsive thiol releasing system for controlling activity of cysteine protease2011

    • Author(s)
      Morishita, K.; Yamaguchi, K.; Ding, H.; Shigenaga, A.; Akaji, K.; Otaka, A
    • Journal Title

      Peptide Science 2010

      Pages: 290

    • Peer Reviewed
  • [Journal Article] Enantioselective synthesis of stimulus-responsive amino acid via asymmetricα-amination of aldehyde2010

    • Author(s)
      Shigenaga, A.; Yamamoto, J.; Nishioka, N.; Otaka, A
    • Journal Title

      Tetrahedron

      Volume: 66 Pages: 7367-7372

    • DOI

      doi:10.1016/j.tet.2010.07.033

    • Peer Reviewed
  • [Journal Article] Development of thiol-responsive amide bond cleavage device and its application for peptide nucleic acid-based DNA releasing system2010

    • Author(s)
      Shigenaga, A.; Yamamoto, J.; Hirakawa, H.; Ogura, K.; Maeda, N.; Morishita, K.; Otaka, A
    • Journal Title

      Tetrahedron Lett

      Volume: 51 Pages: 2525-2528

    • DOI

      doi:10.1016/j.tetlet.2010.03.006

    • Peer Reviewed
  • [Journal Article] Sequential native chemical ligation utilizing peptide thioacids derived from newly developed Fmoc-based synthetic method2010

    • Author(s)
      Shigenaga, A.; Sumikawa, Y.; Tsuda, S.; Sato, K.; Otaka, A
    • Journal Title

      Tetrahedron

      Volume: 66 Pages: 3290-3296

    • DOI

      doi:10.1016/j.tet.2010.03.016

    • Peer Reviewed
  • [Journal Article] Recent Progress in the Synthetic Methodologies of Peptide Thioesters2010

    • Author(s)
      Shigenaga, A.; Sato, K.; Otaka, A
    • Journal Title

      Journal of Synthetic Organic Chemistry Japan

      Volume: 68 Pages: 911-919

    • DOI

      doi:10.5059/yukigoseikyokaishi.68.911

    • Peer Reviewed
  • [Journal Article] A structure-activity relationship study elucidating the mechanism of sequence-specific collagen recognition by the chaperone HSP472010

    • Author(s)
      Nishikawa, Y.; Takahara, Y.; Asada, S.; Shigenaga, A.; Otaka, A.; Kitagawa, K.; Koide, T
    • Journal Title

      Bioorg. Med. Chem

      Volume: 18 Pages: 3767-3775

    • DOI

      doi:10.1016/j.bmc.2010.04.054

    • Peer Reviewed
  • [Journal Article] Proline cis/ trans-Isomerase Pin1 Regulates Peroxisome Proliferator-activated Receptor gamma Activity through the Direct Binding to the Activation Function-1 Domain2010

    • Author(s)
      Fujimoto, Y.; Shiraki, T.; Horiuchi, Y.; Waku, T.; Shigenaga, A.; Otaka, A.; Ikura, T.; Igarashi, K.; Aimoto, S.; Tate, S.; Morikawa, K
    • Journal Title

      J. Biol. Chem

      Volume: 285 Pages: 3126-3132

    • DOI

      doi:10.1074/jbc.M109.055095

    • Peer Reviewed
  • [Journal Article] Structural and functional analyses of minimal phosphopeptides targeting the polo-box domain of polo-like kinase 12009

    • Author(s)
      Yun, S. M.; Moulaei, T.; Lim, D.; Bang, J. K.; Park, J. E.; Shenoy, S. R.; Liu, F.; Kang, Y. H.; Liao, C. Z.; Soung, N. K.; Lee, S.; Yoon, D. Y.; Lim, Y.; Lee, D. H.; Otaka, A.; Appella, E.; McMahon, J. B.; Nicklaus, M. C.; Burke, T. R.; Yaffe, M. B.; Wlodawer, A.; Lee, K. S.
    • Journal Title

      Nature Structural & Molecular Biology

      Volume: 16 Pages: 876-882

    • DOI

      doi:10.1038/nsmb.1628

    • Peer Reviewed
  • [Journal Article] Synthesis of Fluoroalkene Dipeptide Isosteres by an Intramolecular Redox Reaction Utilizing N-Heteorocyclic Carbenes(NHCs)2009

    • Author(s)
      Yamaki, Y.; Shigenaga, A.; Tomita, K.; Narumi, T.; Fujii, N.; Otaka, A
    • Journal Title

      J. Org. Chem

      Volume: 74 Pages: 3272-3277

    • DOI

      doi:10.1021/jo900134k

    • Peer Reviewed
  • [Journal Article] Synthesis of Amide-Type Fluoroalkene Dipeptide Isosteres by an Intramolecular Redox Reaction2009

    • Author(s)
      Yamaki, Y.; Shigenaga, A.; Li, J. L.; Shimohigashi, Y.; Otaka, A
    • Journal Title

      J. Org. Chem

      Volume: 74 Pages: 3278-3285

    • DOI

      doi:10.1021/jo900135t

    • Peer Reviewed
  • [Journal Article] N-> S Acyl-Transfer-Mediated Synthesis of Peptide Thioesters Using Anilide Derivatives2009

    • Author(s)
      Tsuda, S.; Shigenaga, A.; Bando, K.; Otaka, A
    • Journal Title

      Org. Lett

      Volume: 11 Pages: 823-826

    • DOI

      doi:10.1021/ol8028093

    • Peer Reviewed
  • [Journal Article] FRET-based assay of the processing reaction kinetics of stimulus-responsive peptides : influence of amino acid sequence on reaction kinetics2009

    • Author(s)
      Shigenaga, A.; Yamamoto, J.; Hirakawa, H.; Yamaguchi, K.; Otaka, A
    • Journal Title

      Tetrahedron

      Volume: 65 Pages: 2212-2216

    • DOI

      doi:10.1016/j.tet.2009.01.013

    • Peer Reviewed
  • [Journal Article] Fmoc-based solid phase synthesis of adenylylated peptides using diester-type adenylylated amino acid derivatives

    • Author(s)
      Ogura, K.; Shigenaga, A.; Ebisuno, K.; Hirakawa, H.; Otaka, A
    • Journal Title

      Tetrahedron Lett

      Volume: (in press)

    • DOI

      doi:10.1016/j.tetlet.2012.04.063

    • Peer Reviewed
  • [Presentation] N-Sulfanylethylanilides as a Versatile Chemical Device for the Protein Chemistry2012

    • Author(s)
      Otaka, A
    • Organizer
      2012 SNU symposium on Medicinal Chemistry
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2012-05-14
  • [Presentation] Development of amide bond cleavage device with application to chemical biology use2010

    • Author(s)
      Otaka, A.; Shigenaga, A
    • Organizer
      5th International Peptide Symposium in conjunction with 47th Japanese Peptide Symposium
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2010-12-05
  • [Book] 刺激応答型アミノ酸の開発と生命科学分野への応用2012

    • Author(s)
      重永章、山本純、大高章
    • Total Pages
      168-172
    • Publisher
      メディカルドゥ
  • [Book] 第10章最近のペプチド・タンパク質の化学合成について2010

    • Author(s)
      大高章、重永章
    • Total Pages
      205-231
    • Publisher
      建帛社
  • [Remarks]

    • URL

      http://www.tokushima-u.ac.jp/ph/faculty/labo/otaka/

URL: 

Published: 2013-07-31  

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