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

Xiangge Tian, Tao Liu, Yinhua Ma, Jian Gao, Lei Feng, Jingnan Cui, Tony D. James, Xiaochi Ma

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Abstract

UDP-glucuronosyltransferase 1A1 (UGT1A1) is a vital metabolic enzyme responsible for the clearance of endogenous substances and drugs. Hitherto, the 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 a novel “molecular-splicing” strategy to construct a highly selective near-infrared (NIR) fluorescent probe, HHC, for UGT1A1, which exhibited a NIR 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, an isoform-specific NIR fluorescent probe has been developed for monitoring UGT1A1 activity in living systems, high-throughput screening of novel UGT1A1 inhibitors and visual evaluation of bile excretion function.

Original languageEnglish
Pages (from-to)24566-24572
Number of pages7
JournalAngewandte Chemie - International Edition
Volume60
Issue number46
Early online date25 Aug 2021
DOIs
Publication statusPublished - 8 Nov 2021

Bibliographical note

Funding Information:
The authors thank the National Natural Science Foundation of China (81930112, 82004211 and 82104361), National Key R&D Program of China (2018YFC1705900), Liaoning Provincial Key R&D Program (2019JH2/10300022), Dalian Science and Technology Leading Talents Project (2019RD15) and the open Research Fund of the School of Chemistry and Chemical Engineering, Henan Normal University for support (2020ZD01 and 2021YB07) for financial support, T.D.J. wishes to thank the Royal Society for a Wolfson Research Merit Award.

Keywords

  • fluorescence imaging
  • molecular-splicing strategy
  • NIR fluorescent probes
  • UDP-glucuronosyltransferase 1A1

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry

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