Li Qian, Min Jaeki, Ahn Young-Hoon, Namm Joshua, Kim Eun Min, Lui Rowena, Kim Hye Yun, Ji Yong, Wu Hueizhi, Wisniewski Thomas, Chang Young-Tae
Department of Chemistry, New York University, School of Medicine, New York, NY 11219, USA.
Chembiochem. 2007 Sep 24;8(14):1679-87. doi: 10.1002/cbic.200700154.
A group of styryl-based neutral compounds has been synthesized in this study for potential use as in vivo imaging agents for beta-amyloid plaques. Of 56 candidates, 14 compounds were found to label beta-amyloid plaques well on Alzheimer's disease (AD) human brain sections in vitro. The binding affinity to beta-amyloid fibrils was then determined by measuring the change in fluorescence intensity. Interestingly, we found that a class of quinaldine-styryl scaffold compounds displays specific binding to beta-amyloid fibrils. A representative compound, STB-8, was used in ex vivo and in vivo imaging experiments on an AD transgenic mouse model and demonstrated excellent blood-brain barrier (BBB) permeability and specific staining of the AD beta-amyloid plaques.
在本研究中合成了一组基于苯乙烯基的中性化合物，它们有可能用作β-淀粉样蛋白斑块的体内成像剂。在56种候选化合物中，有14种化合物在体外对阿尔茨海默病（AD）人脑切片上的β-淀粉样蛋白斑块标记良好。然后通过测量荧光强度的变化来确定对β-淀粉样蛋白原纤维的结合亲和力。有趣的是，我们发现一类喹哪啶-苯乙烯基支架化合物对β-淀粉样蛋白原纤维具有特异性结合。一种代表性化合物STB-8用于AD转基因小鼠模型的离体和体内成像实验，并表现出优异的血脑屏障（BBB）通透性和对ADβ-淀粉样蛋白斑块的特异性染色。
