A highly selective fluorescent ESIPT probe for the detection of Human carboxylesterase 2 and its biological applications

Lei Feng; Zhao-Ming Liu; Jie Hou; Xia Lv; Jing Ning; Guang-Bo Ge; Jing-Nan Cui; Ling Yang

doi:10.1016/j.bios.2014.10.002

A highly selective fluorescent ESIPT probe for the detection of Human carboxylesterase 2 and its biological applications

Biosens Bioelectron. 2015 Mar 15:65:9-15. doi: 10.1016/j.bios.2014.10.002. Epub 2014 Oct 6.

Authors

Lei Feng¹, Zhao-Ming Liu², Jie Hou³, Xia Lv², Jing Ning⁴, Guang-Bo Ge⁵, Jing-Nan Cui⁶, Ling Yang⁷

Affiliations

¹ State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, China; Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
² Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
³ Dalian Medical University, Dalian 116044, China.
⁴ Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China; Dalian Medical University, Dalian 116044, China.
⁵ State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, China; Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China. Electronic address: geguangbo@dicp.ac.cn.
⁶ State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, China. Electronic address: jncui@dlut.edu.cn.
⁷ Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China. Electronic address: ylingdicp@gmail.com.

PMID: 25461132
DOI: 10.1016/j.bios.2014.10.002

Abstract

A new ratiometric florescence probe derived from 3-hydroxyflavone (3-HF) has been developed for selective and sensitive detection of human carboxylesterase 2 (CE2). The probe is designed by modulating the excited state intramolecular proton transfer (ESIPT) emission of 3-HF via introducing of 4-ethylbenzoyloxy group. Under physiological conditions, probe 1 displays satisfying stability with very low background signal, but it can be selectively hydrolyzed by CE2 to release free 3-HF which brings remarkable changes in fluorescence spectrum. Both reaction phenotyping and chemical inhibition assays demonstrate that probe 1 is highly selective for CE2 over other human hydrolases including carboxylesterase 1, cholinesterases and paraoxonases. Probe 1 has been applied successfully to measure the real activities of CE2 in human biological samples, as well as to screen CE2 inhibitors by using tissue preparations as the enzymes sources. Additionally, probe 1 is cell membrane permeable and can be used for cellular imaging of endogenous CE2 in living cells. All of these features make it possible to serve as a promising tool for exploring the individual differences in biological function of CE2, as well as for rapid screening of selective and potent inhibitors of CE2 for further clinical use.

Keywords: 3-Hydroxylflavone; Bioimaging; Human carboxylesterase 2; Ratiometric fluorescent probe.

MeSH terms

Biosensing Techniques / methods
Carboxylesterase / analysis*
Carboxylesterase / antagonists & inhibitors
Drug Evaluation, Preclinical / methods
Enzyme Assays / methods
Enzyme Inhibitors / pharmacology
Flavonoids / chemistry*
Fluorescent Dyes / chemistry*
HeLa Cells
Humans
Optical Imaging / methods*
Spectrometry, Fluorescence / methods

Substances

Enzyme Inhibitors
Flavonoids
Fluorescent Dyes
CES2 protein, human
Carboxylesterase
3-hydroxyflavone