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Models of the ctiue sites of metalloproteins : synthetic, structural, and functional studies on metallopeptides

Research Project

Project/Area Number 08454213
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Inorganic chemistry
Research InstitutionScience University of Tokyo

Principal Investigator

YAMAMURA Takeshi  Science University of Tokyo, Department of Chemisl Professor, 理学部, 教授 (00114702)

Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥7,700,000 (Direct Cost: ¥7,700,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1997: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1996: ¥4,700,000 (Direct Cost: ¥4,700,000)
KeywordsZinc finger / Cys-X_2-Cys / Zn^<2+>, M^<2+> / hydrolases / His-Glu-X_2-His / Zn^<2+> / molecular dynamics / molecular orbital method / artificial protein / multiple porphyrin / His-Gm-X_2-His / マルチポルフィソン系 / ペプチド / 亜鉛錯体 / リューマチ / プロテインキナーゼC / ポテンショメトリー / 金錯体 / ペプチド錯体 / Cys-X-Y-Cys / Glu-X-Y-His / プロテアーゼ / ペプチドポルフィリン / 会合性 / 構造解析
Research Abstract

1) We prepared the mercury peptide, [(Boc-Cys-Pro-Leu-Cys-Gly-Ala-OMe)Hg], and studied the coordination and conformation structures by EXAFS, ROESY, distance geometry (DG), restrained molecular dynamics (RMD) calculations, -. Comparison of the structure with that of [(Boc-Cys-Pro-Leu-Cys-OMe)Hg] revealed that both of these have a mirror type gamma-tum structure.
2) We clarified the structure of [(Boc-Cys-Pro-Leu-Cys-OMe)(S-tert-C_4H_9)Hg] by the same way as above. This study clarified that the conformation of Cys-X_2-Cys does not depend on the kinds of metal ions, but depends on the S-M-S bite angle, and the peptide conformation obtained for this compound agreed with that of the zinc binding sites of zinc finger motifs
3)We synthesized [(Boc-Cys-Pro-Leu-Cys-OMe)Zn] and [(Boc-Cys-Pro-Leu-Cys-Gly-Ala-OMe)Zn] in terms of zinc finger motifs. We studied the substitution reactions of the zinc sites of these compounds. The structure of the former was discussed by molecular orbital calculations, MD calculations, EXAFS, NMR.
4) We studied the complex formation between Boc-Glu-Thr-Ile-His-OMe and Zn^<2+> with respect to the zinc binding sites of proteases. The structural study by ROESY, RMD and MO suggested that this system generates a species which is structurally similar to the corresponding sites of proteases.
5) We de novo designed and synthesized an artificial protein, which is capable of incorporating multiple porphyrins into its His sites, on the basis of template assisted synthetic protein approach, where a picket fence porphyrin was adopted as the template. This peptide porphyrin incorporated another types of porphyrins into the His sites forming a series of trimeric aggregates, thus achieved a 12 hetero-porphyrin system.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Takeshi Yamamura: "Conformation control of Mode Peptides by Metal Ions, A New Types of Turn Structure Found in [(Bos-Cys-Pro-Leu-Cys-Gly-Ala-OMe)Hg]" Bull.Chem.Soc.Jpn.69. 2221-2230 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hideaki Watanabe,: "Bulky Thiols and Their Coordination Compounds. An Improvement of the Removal of Tetrahydropyranyl Group from Thcols and Its Application for-." Chem.Lett.999-1000 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeshi Yamamura,: "Conformation Control of Peptides by Metal Ions. Coordination Conformation Correlation Ohserned in a Model for Cys-X-Y-Cys/M^<2+> in proteins" Inorg.Chem.36. 4849-4859 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeshi Yamamura,: "Square planar Nickel Compounds with Bulky Thiols" Inong.Chim.Acta. 263. 415-420 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeshi Yamamura,: "Boc-Ghu-Thr-Ile-His-OMe/Zn^<2+> in Terms of the Zlnc-Binding sites of proteases" Inong.Chim.Acta.283. 243-250 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masato Ushiyama,: "Construction of a Multiple porphyrin System Using a denous Designed Peptide Porpryrin and Hemin" Chem.Lett.127-128 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeshi Yamamura, Masaya Arai, Tsutomu Yamane, Takeshi Ukai, Masato Ushiyama, and Hiroshi Hirota: "Conformation Control of Model Peptides by Metal Ions. A New Type of Turn Structure Found in [(Boc-Cys-Pro-Leu-Cys-Gly-Ala-OMe)Hg]" Bull.Chem.Soc.Jpn.69. 2221-2230 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hideaki Watanabe, Seiji Ogo, and Takeshi Yamamura: "Bulky Thiols and Their Coordination Compounds. An Improvement of the Removal of Tetrahydropyranyl Group from Thiols and Its Application for Ligand Syntheses" Chem.Lett.999-1000 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeshi Yamamura, Tsutomu Watanabe, Atsushi Kikuchi, Tsutomu Yamane, Masato Ushiyama, and Hiroshi Hirota: "Conformation Control of Peptides by Metal Ions. Coordination Conformation Correlation Observed in a Model for Cys-X-Y-Cys/M^<2+> in Proteins" Inorg.Chem.36. 4849-4859 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeshi Yamamura, Hideaki Watanabe, Yukiko Niino, Kiyoshi Fujisawa, and Yoshihiko Morooka: "Square Planar Nickel Compounds with Bulky Thiols" Inorg.Chim.Acta. 263. 415-420 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeshi Yamamura, Hidechika Nakamura, Makiko Abe, Tetsuya Sasaki, Masato Ushiyama, Masa-aki Ueki, and Hiroshi Hirota: "Boc-Glu-Thr-Ile-His-OMe/Zn^<2+> in Terms of the Zinc-binding Sites of Proteases" Inorg.Chim.Acta. 283. 243-250 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masato Ushiyama, Fumio Arisaka, and Takeshi Yamamura: "Construction of a Multiple Porphyrin System Using a de novo Designed peptide Porphyrin and Hemin" Chem.Lett.127-128 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masato Ushiyama, Atsushi Yoshino, Takeshi Yamamura, Yasuo Shida, Fumio Arisaka: "A 12-Porphyrin System : Syntheses of Peptide Porphyrins with Multiple Histidines and the Aggregation Behavior in the Presence of Hemin" Bull.Chem.Soc.Jpn.72 (in press.). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hiroteru Nishikawa, Masato Ushiyama, Takeshi Yamamura: "De Novo Designed Heme-binding Peptide-porphyrins. Excitonic Analyses of the UV-vis and CD Spectra" Peptide Science. (in press.). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masato Ushiyama, Hiroteru Nishikawa, Yuka Morio, Takeshi Yamamura: "Construction of Multi Porphyrin Systems Using Histidine Containing 4-Helix Bundle Porphyrin and Heme" Peptide Science. (in press.). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeshi Yamamura,: "Boc-Glu-Thr-Ile-His-OMe/Zn^<2+> in Tenms of the Zinc-Binding Sites of Proteases" Inorg.Chim.Acta. 283. 243-250 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masato Ushiyama,: "Construction of Multiple Porphyrin System Using a denovo Designed Deptide Porphyrin and Hemin" Chem.Lett.127-128 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masato Ushiyama,: "A 12 Porphyrin System:Synthesis of Peptide Porphyrins with Multiple Histidines and the Aggregation Behavior in the Presence of Henin" Bull,Chem.Soc.Jpn.72(inpress). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hiroteru Nishikawa,: "De Nouo Designed Heme-Bincling Peptide Porphyrins.Excltonic Analyses of the UV-vis and CD Spectina" Peptide Science. in press. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masato Ushiyama,: "Consruction of Multi Porphyrin systems Using Histidine Containing 4-Helix Bundle Porphyrin and Heme" Peptide Science. in press. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takeshi Yamamura, et al: "Square Planan Nickel Compounds with Bulky Thiols" Inorg.Chim.Acta. 263. 415-420 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takeshi Yamamura: "Boc-Glu-Thr-Ile-His/Zn^<2+> in terms of Zn-binding sites of Proteases" Inorg.Chim.Acta. (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takeshi Yamamura: "Conformation Control of Peptides by Metal Ions.Coordination Conformation Correlation Observed in a Model for Cys-X-Y-Cys/M^<2+> in Proteins" Inorg.Chem.36. 4849-4859 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] T.Yamamura,M.Arai,T.Yamane,T.Ukai,M.Ushiyama,H.Hitora: "Conformation Controle of Model Peptides by Metal Ions,A New Type of Turn Structure Found in [(Boc-Cys-Pro-Leu-Cys-Gly-Ala-OMe)Hg]" Bull.Chem.Coc.Jpn.69. 2221-2230 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] H.Watanabe,S.Ogo,and T.Yamamura: "Bulky Thiols and Their Coordination Compounds,An Improvement of the Removal of Tetrahydropyranyl Group from Thiols and Its Application-." Chem.Lett.999-1000 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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