具有增强抗Aβ聚合活性的异质对应相关的宏环β片:两个位点比一个更好
Pin-Nan Cheng1, Ryan Spencer, R Jeremy Woods
1Department of Chemistry, University of California, Irvine, Irvine, California 92697-2025, USA.
Journal of the American Chemical Society
|July 26, 2012
概括
与单价或同价版本相比,新的异价宏环在抑制粉样β (Aβ) 聚合方面表现出显著增强的活性. 这些化合物为针对粉样蛋白疾病提供了一个有希望的策略.
科学领域:
- 生物化学 生物化学
- 神经科学是一个神经科学.
- 药用化学 医学化学
背景情况:
- 粉样β (Aβ) 聚合是阿尔茨海默病的标志.
- 开发有效的Aβ聚合抑制剂对于治疗干预至关重要.
研究的目的:
- 合成和评估异对应链的宏环β片,以检测它们在抑制Aβ聚合中的有效性.
- 为了比较异构抑制剂的活性与它们的单价和同构抑制剂的活性.
主要方法:
- 合成单价 (1a,1b),同价 (4,5) 和异价 (6) 相关的宏环β片.
- 提奥夫拉T光测试用于监测Aβ{1-40) 聚合动力学.
主要成果:
- 在等等度下,与异质相对应相关的宏环β片 (6) 显示出Aβ聚合的抑制能力比单价 (1a,1b) 或同质相对应 (4,5) 化合物大6-8倍.
- 观察到显著的聚合延迟,即使在异类抑制剂的亚基基度度.
- 一个拟议的模型表明,异构抑制剂通过多区域相互作用加强与β结构的Aβ寡合体的结合.
结论:
- 与它们的单价和同价类型相比,异对应的宏环β片是Aβ聚合的优质抑制剂.
- 针对氨基类的多重区域的多价抑制剂提供了增强的治疗潜力.
- 这些发现支持开发针对粉样蛋白疾病的多向抑制剂.
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