A Molecular‐Splicing Strategy for Constructing a Near‐Infrared Fluorescent Probe for UDP‐Glucuronosyltransferase 1A1

Abstract

UDP-glucuronosyltransferase 1A1 (UGT1A1) is av ital metabolic enzyme responsible for the clearance of endogenous substances and drugs.H itherto,t he development of fluorescent probes for UGTs was severely restricted due to the poor isoform selectivity and on-off or blue-shifted fluorescence response.Herein, we established anovel "molecular-splicing" strategy to construct ah ighly selective nearinfrared (NIR) fluorescent probe, HHC,f or UGT1A1, which exhibited aN IR signal at 720 nm after UGT1A1 metabolism. HHC was then successfully used for the real-time imaging of endogenous UGT1A1 in living cells and animals and to monitor the bile excretion function. In summary,a ni soformspecific NIR fluorescent probe has been developed for monitoring UGT1A1 activity in living systems,h igh-throughput screening of novel UGT1A1 inhibitors and visual evaluation of bile excretion function.

Fluorescent probes for the detection of disease-associated biomarkers

“…Glycosylation is the process by which glycans are covalently attached to biomolecules (e.g., proteins and lipids) by glycotransferases [185], while, deglycosylation is the removal of saccharides from biomolecules in the presence of glycosidases. Protein glycosylation has been associated with the progression of several diseases, which include cancer, neurodegenerative diseases, lung diseases, blood disorders and genetic disorders.…”

A practical strategy to develop isoform-selective near-infrared fluorescent probes for human cytochrome P450 enzymes

“…Fluorescent probes have been extensively used as useful molecular tools, that can facilitate the noninvasive imaging and dynamic monitoring of enzymatic activity in complex living systems 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 . Imaging probes that exhibit near-infrared (NIR) optical signals have many advantages including minimal interference from tissue autofluorescence and improved tissue penetration, which facilitates imaging allowing for accurate activity monitoring of functional proteins in living systems 28 , 29 , 30 , 31 , 32 , 33 . However, to date the number of selective NIR fluorescent probes for real-time imaging of various CYP isoforms are limited.…”