化学
丁酰胆碱酯酶
体内
荧光团
生物标志物
乙酰胆碱酯酶
药理学
生物化学
荧光
阿切
酶
量子力学
物理
医学
生物技术
生物
作者
Lei Wang,Tianyu Sun,Tiantian Zhen,Wei Li,Huajing Yang,Suyu Wang,Feng Feng,Yao Chen,Haopeng Sun
标识
DOI:10.1021/acs.jmedchem.4c00355
摘要
Butyrylcholinesterase (BChE) is a promising biomarker and effective therapeutic target for Alzheimer's disease (AD). Herein, we designed a BChE-activated near-infrared (NIR) probe, DTNP, which could be activated by BChE and inhibit its enzymatic activity. DTNP is composed of a cyclopropane moiety as the recognition unit, a NIR fluorophore hemicyanine as the NIR reporter, and a BChE inhibitor as the therapeutic unit. DTNP specifically binds BChE with high sensitivity and exhibits strong "turn-on" NIR fluorescence as well as nerve cell protection. In vivo imaging shows DTNP has favorable blood-brain barrier permeability and long-term tracking ability with preliminary competence in AD diagnosis. DTNP can significantly inhibit BChE activity, promote the release of ACh, and rescue learning deficits and cognitive impairment. Therefore, DTNP, the first reported and partially validated theranostic probe for the detection of BChE in AD, may provide a foundation and inspiration for imaging and therapy in AD.
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