A new near-infrared fluorescence probe for highly selective and sensitive detection and imaging of Butyrylcholinesterase in Alzheimer's disease mice

Jian Zhang; Xiaojie Tang; Honglan Qi; Zhao Li; Xiaowei He

doi:10.1016/j.talanta.2024.127377

A new near-infrared fluorescence probe for highly selective and sensitive detection and imaging of Butyrylcholinesterase in Alzheimer's disease mice

Talanta. 2024 Dec 14:285:127377. doi: 10.1016/j.talanta.2024.127377. Online ahead of print.

Authors

Jian Zhang¹, Xiaojie Tang², Honglan Qi³, Zhao Li⁴, Xiaowei He⁵

Affiliations

¹ The School of Information Sciences and Technology, Northwest University, Xi'an, 710127, China.
² Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, 710062, China.
³ Key Laboratory of Analytical Chemistry for Life Science of Shaanxi Province, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an, 710062, China.
⁴ Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, 710062, China. Electronic address: lizhao0309@snnu.edu.cn.
⁵ The School of Information Sciences and Technology, Northwest University, Xi'an, 710127, China. Electronic address: hexw@nwu.edu.cn.

PMID: 39706039
DOI: 10.1016/j.talanta.2024.127377

Abstract

Butylcholinesterase (BChE) is a key enzyme in living system, closely related to liver and neurological diseases. It is very challenge to develop near-infrared (NIR) fluorescence probe methods for highly selective and sensitive detection of BChE in vivo. Based on the differences in active sites and spatial pockets between acetylcholinesterase (AChE) and BChE, a new NIR BChE-responsive fluorescence probe Probe-BChE (λ_ex/λ_em = 600 nm/676 nm) was designed and synthesized by introducing dimethyl carbamate group as recognizing moiety to a NIR fluorophore hemicyanine skeleton. It was found that Probe-BChE specifically binds with BChE, rather than AChE, since BChE has a big cavity and strong intermolecular forces with Probe-BChE, which was supported by the molecular docking scores. The fluorescence method for the determination of BChE was developed with a detection limit of 0.14 U/mL BChE and high selectivity as well as short reaction time (∼3 s). The fluorescence imaging method using Probe-BChE efficiently image the levels of endogenous BChE in brains and main organs (heart, liver, spleen, lung and kidney) of Alzheimer's disease (AD) mice. The results reveal that the levels of endogenous BChE in old AD mice is higher than that in young AD mice, and endogenous BChE is enriched in the liver of AD mice. This work demonstrates that Probe-BChE is a promising fluorescence probe for imaging of endogenous BChE in AD mice. The design of NIR fluorescence probes for endogenous BChE in this work will promote to design NIR fluorescence probes for endogenous cholinesterase.

Keywords: Alzheimer's disease; Butylcholinesterase; Fluorescence probe; Imaging analysis; Mice.