| Project/Area Number |
17310132
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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 |
Living organism molecular science
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| Research Institution | Toho University |
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Principal Investigator |
OKUNO Hiroaki Toho University, Faculty of Pharmaceutical Sciences, Professor (20356710)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Hideharu Toho University, Faculty of Pharmaceutical Sciences, Lecturer (40187753)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥12,970,000 (Direct Cost: ¥12,100,000、Indirect Cost: ¥870,000)
Fiscal Year 2007: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2006: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2005: ¥6,200,000 (Direct Cost: ¥6,200,000)
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| Keywords | amyloid β pentide / aggregation inhibitor / in vitro activity / quartz-crystal microbalance / in vivo activity / transgenic mouse / Alzet / 水晶発振子マイクロバランス |
|---|
| Research Abstract |
A series of amyloid- aggregation inhibitors composed of a molecular recognition element (KLVFF) and an aggregation-disrupting part (having an electrostatic and hydrophilic nature) based on amino acid analogs have been synthesized. A quartz-crystal microbalance (QCM) method was applied and found to be very successful in evaluating the inhibitory activity of the AP aggregation, which was observed when the frequency was increased. The QCM can detect a mass change with differences in frequency that correspond to a 1 Hz frequency decrease per 30 pg mass increase on a 4.9 mm^2 electrode. Furthermore, bioassay results showed no toxicity of the inhibitor itself against IMR-32 neuroblastoma cells, and remarkably reduced cytotoxicities of both Aβ1-40 and Aβ1-42 were exhibited in the presence of these inhibitors. The KLVFF- (EEX) 3 derivative was the most efficient Aβ aggregation among the inhibitors examined here.
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