Highly Sensitive Near-Infrared Fluorophores for in Vivo Detection of Amyloid-尾 Plaques in Alzheimer鈥檚 Disease

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• 作者：Hualong Fu ; Mengchao Cui ; Liu Zhao ; Peiyu Tu ; Kaixiang Zhou ; Jiapei Dai ; Boli Liu
• 刊名：Journal of Medicinal Chemistry
• 出版年：2015
• 出版时间：September 10, 2015
• 年：2015
• 卷：58
• 期：17
• 页码：6972-6983
• 全文大小：650K
• ISSN：1520-4804

文摘

Alzheimer鈥檚 disease (AD) is pathologically characterized by the accumulation of 尾-amyloid (A尾) deposits in the parenchymal and cortical brain. In this work, we designed, synthesized, and evaluated a series of near-infrared (NIR) probes with electron donor鈥揳cceptor end groups interacting through a 蟺-conjugated system for the detection of A尾 deposits in the brain. Among these probes, 3b and 3c had excellent fluorescent properties (emission maxima > 650 nm and high quantum yields) and displayed high sensitivity and high affinities to A尾 aggregates (3b, K_d = 8.8 nM; 3c, K_d = 1.9 nM). Both 3b and 3c could readily penetrate the blood鈥揵rain barrier with high initial brain uptake and fast to moderate washout from the brain. In vivo NIR imaging revealed that 3b and 3c could efficiently differentiate transgenic and wild-type mice. In summary, our research provides new hints for developing smarter and more activatable NIR probes targeting A尾.