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Structural investigations for developing the rapeutics of Altzheimer, prion, and Parkinson's disease

Research Project

Project/Area Number 13672251
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Physical pharmacy
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

KURODA Yoshihiro  Kyoto Univ, Grad. School of Pharm. Sci. Associate Professor, 薬学研究科, 助教授 (90093236)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsAltzheimer disease / Prion disease / Parkinson's disease / α helix / β sheet / amyloid / oligopeptide / CD spectra
Research Abstract

1. In order to obtain insight how to find out oligqpeptides from the amino acid sequences of A β, PrP, and NAG, oligopeptidemediated helix stabilization of Na channel related peptides has been studied. It was found that oligopeptides should involve hydrophobic amino acids and should be interposed by such polar amino acids as lysine for stabilizing α-helices of the model peptides
2. By designing various kinds of oligopeptides from the amino acid sequence of A β, interactions between oligopeptides and Aβ have been studied. Among the oligopeptides studied, only Ac-ELVFFAKK-NH_2 was found to increase β-sheet content and accelerate amyloid fibril formation
3. I have selected PrP(129-154) and PrP(192-213) from PrP and studied interactions with the oligopeptides designed from those peptides. Ac-EFGNK-NH_2 and Ac-EYYEK-NH_2 stabilized α-helices of PrP(129-154), but every oligopeptides studied destabilized α-helix of PrP(192-213)
4. The peptide Ac-ETVK-NH_2 increased the β-sheet content of NAG in water and accelerated amyloid fibril formation
5. If an oligopeptide involves a fragment of amyloidogenic proteins and destabilizes their α-helices, the peptide could be a trigger to initiate amyloid diseases

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Yoshitaka Maeda: "Helix-stabilizing effects of the pentapeptide KIFMK and its related Peptides on the sodium channel inactivation gate peptides"J. Peptide Res.. 58・5. 413-423 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kazuhide Miyamoto: "Solution structure of the cytoplasmic linker between domain III-S6 and domain IV-S1 (III-IV linker) of the rat brain sodium channel in SDS micelles"Biopolymers. 59・5. 380-393 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kazuhide Miyamoto: "Solution structures of the cytoplasmic linkers between segments S4 and S5 (S4-S5) in domains III and IV of human brain sodium Channels in SDS micelles"J. Peptide Res.. 58・3. 193-203 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshitaka Maeda: "Oligopeptide-mediated helix stabilization of model peptides in aqueous solution"J. Peptide Sci.. 9・2. 106-113 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshihiro Kuroda: "Effects of detergents on the secondary structures of prion protein peptides as studied by CD spectroscopy"J. Peptide Sci.. 9・4. 212-220 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshihiro Kuroda: "Oligopeptide-mediated acceleration of amyloid fibril formation of amyloidβ and β) and α-synuclein fragment peptide (NAC)"J. Peptide Sci.. 9(印刷中). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y. Maeda, T. Nakagawa, and Y. Kuroda: "Helix-stabilizing effects of the pentapeptide KIFMK aud its related peptides on the sodium channel inactivation gate peptides"J. Peptide Res.. 58(5). 413-423 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K. Miyamoto, T. Nakagawa, and Y. Kuroda: "Solution structure of the cytoplasmic linker between domain III-S6 and domain IV-S1(III-IV linker) of the rat brain soditim channel in SDS micelles"Biopolymers. 59(5). 380-393 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K. Miyamato, T. Nakagawa, and Y. Kuroda: "Solution structures of the cytoplasmic linkers between segments S4 and S5 (S4-S5) in domains III and IV of human brain sodium channels in SDS micelles"J. Peptide Res.. 58(3). 193-203 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y. Maeda, T. Nakagawa, and Y. Kuroda: "Oligopeptide-mediated helix stabilization of model peptides in aqueous solution"J. Peptide Sci.. 9(2). 106-113 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y. Kuroda, Y. Maeda, S. Sawa, K. Shibata, K. Miyamoto, and T. Nakagawa: "Effects of detergents on the secondary structures of prion piotein peptides as studied by CD spectroscopy"J. Peptide Sci.. 9(4). 212-220 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y. Kuroda, Y. Maeda, H. Hanaoka, K. Miyamoto, and T. Nakagawa: "Oligopeptide-mediated acceleration of amyloid fibril formation of amyloid β(Aβ) and α-synuclein fragment peptide (NAG)"J. Peptide Sci.. 9 (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshitaka Maeda: "Oligopeptide-mediated helix stabilization of medel peptides in aqueous solution"J. Peptide Sci.. 9・2. 106-113 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshihiro Kuroda: "Effects of detergents on the secondary structures of prion protein peptides as studied by CD spectroscopy"J. Peptide Sci.. 9(印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kazuhide Miyamoto: "Solution structure of the cytoplasmic linker between domain III-S6 and domain IV-S1 (III-IV linker) of the rat brain sodium channel in SDS micelles"Biopolymers. 57・5. 380-393 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kazuhide Miyamoto: "Solution structures of the cytoplasmic linkers between segments S4 and S5 (S4-S5) in domains III and IV of human brain sodium Channels in SDS micelles"J. Peptide Res.. 58・3. 193-203 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshitaka Maeda: "Helix-stabilizing effects of the pentapeptide KIFMK and its related Peptides on the sodium channel inactivation gate peptides"J. Peptide Res.. 58・5. 413-423 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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