A Molecular Approach to Rationally Constructing Specific Fluorogenic Substrates for the Detection of Acetylcholinesterase Activity in Live Cells, Mice Brains and Tissues

Overview

Journal Chem Sci

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2021 Jun 7

PMID 34094370

Citations 7

Authors

Xiaofeng Wu

Jong Min An

Jizhen Shang

Eugene Huh

Sujie Qi

Eunhye Lee

Haidong Li

Gyoungmi Kim

Huimin Ma

Myung Sook Oh

Dokyoung Kim

Juyoung Yoon

Affiliations

Soon will be listed here.

Abstract

Acetylcholinesterase (AChE) is an extremely critical hydrolase tightly associated with neurological diseases. Currently, developing specific substrates for imaging AChE activity still remains a great challenge due to the interference from butyrylcholinesterase (BChE) and carboxylesterase (CE). Herein, we propose an approach to designing specific substrates for AChE detection by combining dimethylcarbamate choline with a self-immolative scaffold. The representative can effectively eliminate the interference from CE and BChE. The high specificity of has been proved imaging AChE activity in cells. Moreover, can also be used to successfully map AChE activity in different regions of a normal mouse brain, which may provide important data for AChE evaluation in clinical studies. Such a rational and effective approach can also provide a solid basis for designing probes with different properties to study AChE in biosystems and another way to design specific substrates for other enzymes.

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References

Mutze J, Iyer V, Macklin J, Colonell J, Karsh B, Petrasek Z . Excitation spectra and brightness optimization of two-photon excited probes. Biophys J. 2012; 102(4):934-44. PMC: 3283774. DOI: 10.1016/j.bpj.2011.12.056. View

Liu S, Xiong H, Yang J, Yang S, Li Y, Yang W . Discovery of Butyrylcholinesterase-Activated Near-Infrared Fluorogenic Probe for Live-Cell and In Vivo Imaging. ACS Sens. 2018; 3(10):2118-2128. DOI: 10.1021/acssensors.8b00697. View

Zhang X, Yang L, Zhao Q, Caen J, He H, Jin Q . Induction of acetylcholinesterase expression during apoptosis in various cell types. Cell Death Differ. 2002; 9(8):790-800. DOI: 10.1038/sj.cdd.4401034. View

Liederer B, Borchardt R . Enzymes involved in the bioconversion of ester-based prodrugs. J Pharm Sci. 2006; 95(6):1177-95. DOI: 10.1002/jps.20542. View

Sussman J, Harel M, Frolow F, Oefner C, Goldman A, Toker L . Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein. Science. 1991; 253(5022):872-9. DOI: 10.1126/science.1678899. View

Yoo S, Han M . A fluorescent probe for butyrylcholinesterase activity in human serum based on a fluorophore with specific binding affinity for human serum albumin. Chem Commun (Camb). 2019; 55(97):14574-14577. DOI: 10.1039/c9cc07737e. View

Wang R, Chen J, Gao J, Chen J, Xu G, Zhu T . A molecular design strategy toward enzyme-activated probes with near-infrared I and II fluorescence for targeted cancer imaging. Chem Sci. 2019; 10(30):7222-7227. PMC: 6677112. DOI: 10.1039/c9sc02093d. View

Soreq H, Seidman S . Acetylcholinesterase--new roles for an old actor. Nat Rev Neurosci. 2001; 2(4):294-302. DOI: 10.1038/35067589. View

Savelieff M, Nam G, Kang J, Lee H, Lee M, Lim M . Development of Multifunctional Molecules as Potential Therapeutic Candidates for Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis in the Last Decade. Chem Rev. 2018; 119(2):1221-1322. DOI: 10.1021/acs.chemrev.8b00138. View

10.

Zhang Y, Chen W, Feng D, Shi W, Li X, Ma H . A spectroscopic off-on probe for simple and sensitive detection of carboxylesterase activity and its application to cell imaging. Analyst. 2011; 137(3):716-21. DOI: 10.1039/c2an15952j. View

11.

Chen J, Liao D, Wang Y, Zhou H, Li W, Yu C . Real-time fluorometric assay for acetylcholinesterase activity and inhibitor screening through the pyrene probe monomer-excimer transition. Org Lett. 2013; 15(9):2132-5. DOI: 10.1021/ol400619t. View

12.

Li H, Li Y, Yao Q, Fan J, Sun W, Long S . imaging of aminopeptidase N activity in hepatocellular carcinoma: a migration model for tumour using an activatable two-photon NIR fluorescent probe. Chem Sci. 2019; 10(6):1619-1625. PMC: 6368242. DOI: 10.1039/c8sc04685a. View

13.

Jin R, Xing Z, Kong D, Yan X, Liu F, Gao Y . Sensitive colorimetric sensor for point-of-care detection of acetylcholinesterase using cobalt oxyhydroxide nanoflakes. J Mater Chem B. 2020; 7(8):1230-1237. DOI: 10.1039/c8tb02987c. View

14.

Feng F, Tang Y, Wang S, Li Y, Zhu D . Continuous fluorometric assays for acetylcholinesterase activity and inhibition with conjugated polyelectrolytes. Angew Chem Int Ed Engl. 2007; 46(41):7882-6. DOI: 10.1002/anie.200701724. View

15.

Liu D, Chen W, Wei J, Li X, Wang Z, Jiang X . A highly sensitive, dual-readout assay based on gold nanoparticles for organophosphorus and carbamate pesticides. Anal Chem. 2012; 84(9):4185-91. DOI: 10.1021/ac300545p. View

16.

Liu H, Li K, Hu X, Zhu L, Rong Q, Liu Y . In Situ Localization of Enzyme Activity in Live Cells by a Molecular Probe Releasing a Precipitating Fluorochrome. Angew Chem Int Ed Engl. 2017; 56(39):11788-11792. DOI: 10.1002/anie.201705747. View

17.

Cui K, Chen Z, Wang Z, Zhang G, Zhang D . A naked-eye visible and fluorescence "turn-on" probe for acetyl-cholinesterase assay and thiols as well as imaging of living cells. Analyst. 2010; 136(1):191-5. DOI: 10.1039/c0an00456a. View

18.

Potter P, Pawlik C, Morton C, Naeve C, Danks M . Isolation and partial characterization of a cDNA encoding a rabbit liver carboxylesterase that activates the prodrug irinotecan (CPT-11). Cancer Res. 1998; 58(12):2646-51. View

19.

Zhou G, Wang F, Wang H, Kambam S, Chen X, Yoon J . Colorimetric and fluorometric assays based on conjugated polydiacetylene supramolecules for screening acetylcholinesterase and its inhibitors. ACS Appl Mater Interfaces. 2013; 5(8):3275-80. DOI: 10.1021/am400260y. View

20.

Wang X, Li P, Ding Q, Wu C, Zhang W, Tang B . Observation of Acetylcholinesterase in Stress-Induced Depression Phenotypes by Two-Photon Fluorescence Imaging in the Mouse Brain. J Am Chem Soc. 2019; 141(5):2061-2068. DOI: 10.1021/jacs.8b11414. View