Cao Yangyang, Liu Xiaohui, Zhang Jingjing, Liu Zhongmin, Fu Yan, Zhang Dong, Zheng Mingyue, Zhang Haiyan, Xu Ming-Hua
Shenzhen Grubbs Institute and Department of Chemistry, Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen 518055, China.
CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
ACS Chem Neurosci. 2023 Mar 1;14(5):829-838. doi: 10.1021/acschemneuro.2c00468. Epub 2023 Feb 7.
Amyloid-β (Aβ) is the core constituent protein of senile plaques, which is one of the key pathological hallmarks of Alzheimer's disease (AD). Here we describe the design, synthesis, and evaluation of coumarin-derived small molecule fluorophores for Aβ imaging. By embedding the aromatic coumarin framework into π bridge of a push-pull chromophore, a novel fluorescence probe applicable to efficient Aβ recognition was discovered. displays higher fluorescent enhancement for aggregated Aβ than monomeric Aβ, and possesses good blood-brain barrier permeability. staining and imaging studies demonstrated that could efficiently recognize Aβ plaques in the brain of AD transgenic mice. These results suggest that is a promising fluorescence imaging agent for Aβ, which might provide important clues for the future development of potent NIR fluorescent probes for Aβ diagnosis.
淀粉样β蛋白（Aβ）是老年斑的核心组成蛋白，老年斑是阿尔茨海默病（AD）的关键病理特征之一。在此，我们描述了用于Aβ成像的香豆素衍生小分子荧光团的设计、合成及评估。通过将芳香香豆素骨架嵌入推拉发色团的π桥中，发现了一种适用于高效Aβ识别的新型荧光探针。该探针对聚集态Aβ的荧光增强高于单体Aβ，且具有良好的血脑屏障通透性。染色和成像研究表明，该探针能够有效识别AD转基因小鼠脑中的Aβ斑块。这些结果表明，该探针是一种有前景的Aβ荧光成像剂，可能为未来开发用于Aβ诊断的高效近红外荧光探针提供重要线索。
