Structural investigations for developing the rapeutics of Altzheimer, prion, and Parkinson's disease
| Project/Area Number |
13672251
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Physical pharmacy
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
KURODA Yoshihiro Kyoto Univ, Grad. School of Pharm. Sci. Associate Professor, 薬学研究科, 助教授 (90093236)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| 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)
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| Keywords | Altzheimer disease / Prion disease / Parkinson's disease / α helix / β sheet / amyloid / oligopeptide / CD spectra |
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| 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
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Report
(3 results)
Research Products
(17 results)
