University of Chinese Academy of Sciences , Beijing , 100049 , China.
College of Pharmaceutical Sciences , Zhejiang University , Hangzhou , 310058 , China.
Bioconjug Chem. 2018 Oct 17;29(10):3459-3466. doi: 10.1021/acs.bioconjchem.8b00623. Epub 2018 Sep 18.
Fluorescent imaging of β-amyloid (Aβ) is one of the most promising methods for Alzheimer's disease diagnosis. Several fluorescent probes have been reported to detect Aβ both in vitro and in vivo. However, highly sensitive and highly selective probes with low background signals are still greatly needed. Herein, we rationally designed and synthesized a PIET quenched near-infrared probe QAD-1 to detect Aβ. This probe contains BODIPY as fluorophore and tetrahydroquinoxaline as the quenching group. QAD-1 exhibited significant fluorescent switch-on after binding to soluble and insoluble Aβ species, and the probe had the benefit of low background signal to stain Aβ plaques without the need of wash-out procedures in vitro, which was specially found by the fluorescence off-on probe. QAD-1 could identify the overproduced Aβ in transgenic (APP/PSEN 1dE9) AD mice as early as 6 months old in vivo, which indicated that QAD-1 may be a potential probe for monitoring Aβ species at an early stage of AD.
荧光成像β-淀粉样蛋白（Aβ）是阿尔茨海默病诊断最有前途的方法之一。已经有报道称，有几种荧光探针可用于体外和体内检测 Aβ。然而，仍然非常需要具有低背景信号的高灵敏度和高选择性探针。在此，我们合理设计并合成了一种 PIET 猝灭近红外探针 QAD-1 来检测 Aβ。该探针以 BODIPY 作为荧光团，以四氢喹喔啉作为猝灭基团。QAD-1 在与可溶性和不溶性 Aβ 物种结合后表现出显著的荧光开启，并且该探针具有低背景信号的优点，可以在体外无需冲洗程序即可对 Aβ斑块进行染色，这是荧光关闭-开启探针特别发现的。QAD-1 可以在体内尽早识别出转基因（APP/PSEN 1dE9）AD 小鼠中过度产生的 Aβ，这表明 QAD-1 可能是监测 AD 早期 Aβ 物种的潜在探针。
