| Project/Area Number |
12470489
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 |
TAGA Tooru Grad. Sch. Pharm. Sci, KYOTO UNIVERSITY, Prof., 薬学研究科, 教授 (00025694)
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| Co-Investigator(Kenkyū-buntansha) |
KURODA Yoshihiro Grad. Sch. Pharm. Sci, KYOTO UNIVERSITY, Prof., 薬学研究科, 助教授 (90093236)
HONDA Tetsuro Grad. Sch. Pharm. Sci, KYOTO UNIVERSITY, Prof., 薬学研究科, 教授 (00025719)
NAKAGAWA Teramichi Grad. Sch. Pharm. Sci, KYOTO UNIVERSITY, Prof., 薬学研究科, 教授 (70025708)
MATSUMOTO Osamu Grad. Sch. Pharm. Sci, KYOTO UNIVERSITY, Prof., 薬学研究科, 助教授 (10231599)
SHIBUKAWA Akimasa Grad. Sch. Pharm. Sci, KYOTO UNIVERSITY, Prof., 薬学研究科, 助教授 (30170913)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥13,700,000 (Direct Cost: ¥13,700,000)
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| Keywords | SPR / Biosuper molecular Assembly / Highly fine structure / high performance fromtall Analysis / low density lipo-protein / apo A-1 / any loid / Monte Carlo-cal / 表面ブラズモン共鳴 / apoA-1 / 表面プラスモン共鳴 / 低密度血漿リポタンパク質 / 脂質2分子層 / 血漿アポリポタンパク質 / レセプター / アルツハイマー / シミュレーション |
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| Research Abstract |
In this project, we performed several researches about the highly detailed structure and the function on a bio-supermolecular assembly which are shown in lower (1) - (5).
(1) The binding study using high-performance frontal analysis found that the oxidation of low-density lipoprotein (LDL) enhances the drug binding affinity of LDL, and the increase in negative net charge due to LDL oxidation gives significant effect upon this binding enhancement. It was also found that the major genetic variants of AGP show different drug binding property, and their drug binding affinity and the enantioselectivity strongly depend upon the pH condition of sample solution.
(2) Interaction and activation of plasma apolipoproteins A-1 and E at lipid particle surface were influenced by the amphipathic surface topology. Not only surface but core lipid composition of particles played roles in the topology-formation.
(3) We examined the Gi activity of partial peptides of a Prostaglandin and an Opioid receptors, a
… More
nd the molecular interactions. All peptides formed the stable complex with Gi and activated G protein further. As a result of NMR structural analysis, the helix structure is found on the N-terminal.The potion forms a positive charge cluster and is thought that it activates G protein.
(4) The effects of small peptides on the secondary structures of the peptides dissected from such amyloidgenic proteins as Aβ(Alzheimer's sisease), α-synuclein/NAC (Parkinson's disease), and PrP (prion disease) were studied. It was found that Ac-ELVFFAKK-NH_2 in Aβ(1-28), Ac-ETVK-NH_2 and Ac-KTVE-NH_2 in NAC(19-35), and Ac-EFGNK-NH_2 in and Ac-EYYEK-NH_2 in PrP(129-154) interact specifically with the peptides. Each of these small peptides could be a lead compound for designing a therapeutic agent for the diseases.
(5) The statistical properties of the curved bilayer membranes of DPPC and the interactions of vitamin E with the planar membranes of DPPC in the liquid-crystal phase were studied by Monte-Calro simulation. Less
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