title: A highly selective fluorescent ESIPT probe for the detection of Human carboxylesterase 2 and its biological applications.
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.
authors.affiliation: 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.
authors.forename: Lei
authors.initials: L
authors.lastname: Feng
authors.affiliation: Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
authors.forename: Zhao-Ming
authors.initials: ZM
authors.lastname: Liu
authors.affiliation: Dalian Medical University, Dalian 116044, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Hou
authors.affiliation: Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Lv
authors.affiliation: Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China; Dalian Medical University, Dalian 116044, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ning
authors.affiliation: 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.
authors.forename: Guang-Bo
authors.initials: GB
authors.lastname: Ge
authors.affiliation: State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, China. Electronic address: jncui@dlut.edu.cn.
authors.forename: Jing-Nan
authors.initials: JN
authors.lastname: Cui
authors.affiliation: Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China. Electronic address: ylingdicp@gmail.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Yang
mesh_terms: D015374:Biosensing Techniques / Q000379:methods; D043182:Carboxylesterase / Q000032:analysis* / Q000037:antagonists & inhibitors; D004353:Drug Evaluation, Preclinical / Q000379:methods; D057075:Enzyme Assays / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D061848:Optical Imaging / Q000379:methods*; D013050:Spectrometry, Fluorescence / Q000379:methods
chemical_list: D004791:Enzyme Inhibitors; D005419:Flavonoids; D005456:Fluorescent Dyes; C517204:CES2 protein, human; D043182:Carboxylesterase; C041477:3-hydroxyflavone
keywords: 3-Hydroxylflavone; Bioimaging; Human carboxylesterase 2; Ratiometric fluorescent probe