An Optimized Two‐Photon Fluorescent Probe for Biological Sensing and Imaging of Catechol‐O‐Methyltransferase

• Published in: Chemistry : a European journal Vol. 23; no. 45; pp. 10800 - 10807
• Main Authors: Wang, Ping, Xia, Yang‐Liu, Zou, Li‐Wei, Qian, Xing‐Kai, Dou, Tong‐Yi, Jin, Qiang, Li, Shi‐Yang, Yu, Yang, Wang, Dan‐Dan, Luo, Qun, Ge, Guang‐Bo, Yang, Ling
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 10.08.2017; Wiley Subscription Services, Inc
• Subjects: Animals; Binding Sites; bio-imaging; Biological activity; Biological properties; Biological samples; biosensing; Brain - metabolism; Catechol; Catechol O-methyltransferase; Catechol O-Methyltransferase - chemistry; Catechol O-Methyltransferase - metabolism; Cell Line, Tumor; Cell permeability; Cells (biology); Chemistry; Chemistry, Multidisciplinary; coumarins; Coumarins - chemical synthesis; Coumarins - chemistry; Coumarins - metabolism; Cytotoxicity; Enzymes; Fluorescence; Fluorescent Dyes - chemical synthesis; Fluorescent Dyes - chemistry; Fluorescent Dyes - metabolism; Fluorescent indicators; Humans; Image resolution; Imaging; Kinetics; Methylation; Methyltransferase; Microscopy, Fluorescence, Multiphoton; Molecular Docking Simulation; Photons; Physical Sciences; Rats; Science & Technology; Selectivity; Spectrometry, Fluorescence; Toxicity; METHYLATION; DESIGN; coumarins; SCHIZOPHRENIA; DISORDERS; POLYMORPHISM; COMT; bio-imaging; catechol-o-methyltransferase; fluorescence; biosensing; NITRIC-OXIDE; INHIBITORS; PARKINSONS-DISEASE; LIVING CELLS
• DOI: 10.1002/chem.201701384
• ISSN: 0947-6539; 1521-3765

A practical two‐photon fluorescent probe was developed for highly sensitive and selective sensing of the activities of catechol‐O‐methyltransferase (COMT) in complex biological samples. To this end, a series of 3‐substituted 7,8‐dihydroxycoumarins were designed and synthesized. Among them, 3‐BTD displayed the best combination of selectivity, sensitivity, reactivity, and fluorescence response following COMT‐catalyzed 8‐O‐methylation. The newly developed two‐photon fluorescent probe 3‐BTD can be used for determining the activities of COMT in complex biological samples and bio‐imaging of endogenous COMT in living cells and tissue slices with good cell permeability, low cytotoxicity, and high imaging resolution. All these findings suggest that 3‐BTD holds great promise for developing therapeutic molecules that target COMT, as well as for exploring COMT‐associated biological processes and its biological functions in living systems. Furthermore, the strategy also sheds new light on the development of fluorescent probes for other conjugative enzymes. A bright two‐photon fluorescent probe 3‐BTD for catechol‐O‐methyltransferase (COMT) is developed and characterized. 3‐BTD can be used for real‐time monitoring of COMT activities in complex biological samples and bio‐imaging of endogenous COMT in living systems with good cell permeability, low cytotoxicity, and high imaging resolution.