Development of aggregation disrupters for amyloid proteins

淀粉样蛋白聚集破坏剂的开发

• 批准号: 17310132
• 负责人: OKUNO Hiroaki
• 金额: $ 8.3万
• 依托单位: Toho University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17310132/
• 关键词: 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

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.

已经合成了一系列基于氨基酸类似物的淀粉样蛋白聚集抑制剂，其由分子识别元件（KLVFF）和聚集破坏部分（具有静电和亲水性质）组成。应用石英晶体微天平（QCM）方法，发现其在评估AP聚集的抑制活性方面非常成功，当频率增加时观察到该抑制活性。QCM可以检测到质量变化的频率差异，对应于4.9 mm^2电极上每增加30 pg质量，频率降低1 Hz。此外，生物测定结果表明，抑制剂本身对IMR-32神经母细胞瘤细胞没有毒性，并且在存在这些抑制剂的情况下，Aβ1-40和Aβ1-42的细胞毒性均显著降低。KLVFF-（EEX）3衍生物是此处检查的抑制剂中最有效的Aβ聚集剂。

项目成果

Convenient Method for Monitoring Aβ Aggregation bi Quartz-Crystal Microbalance

双石英晶体微天平监测 Aβ 聚集的便捷方法

• 发表时间: 2006
• 期刊: Chemical Biology ＆ Drug Design 68
• 作者: hiroaki Okuno;Kanae Mori;Tomofumi jitsukawa;Hiromi Inoue;S. Chiba
• 通讯作者: S. Chiba

Development of aggregation inhibitors for amyloid-β peptides and their evaluation by quartz-crystal microbalance

• DOI: 10.1111/j.1747-0285.2007.00509.x
• 发表时间: 2007-05-01
• 期刊: CHEMICAL BIOLOGY & DRUG DESIGN
• 影响因子: 3
• 作者: Okuno, Hiroaki;Mori, Kanae;Suzuki, Hideharu
• 通讯作者: Suzuki, Hideharu

An improved synthesis of optically pure (R)-4-bromo-N-methyl-1-tosyltryptophan derivative, a key intermediate in the synthesis of ergot alkaloids

光学纯 (R)-4-溴-N-甲基-1-甲苯磺酰色氨酸衍生物的改进合成，该衍生物是合成麦角生物碱的关键中间体

• 发表时间: 2005
• 期刊: Heterocycles 65
• 作者: Yokoyama Y;Hara R;Kato N;Murakami Y;Okuno H
• 通讯作者: Okuno H

Synthesis of amyloid aggregation inhibitors&its evaluation by QCM

淀粉样蛋白聚集抑制剂的合成

• 发表时间: 2007
• 期刊: Alzheimer's Disease:New Advances
• 作者: Okuno;Mori;Okada
• 通讯作者: Okada

アミロイドベータ凝集阻害作用を有するフェノール誘導体

抑制β淀粉样蛋白聚集的苯酚衍生物

• 发表时间: 2008