TY - JOUR
T1 - A Molecular-Splicing Strategy for Constructing a Near-Infrared Fluorescent Probe for UDP-Glucuronosyltransferase 1A1
AU - Tian, Xiangge
AU - Liu, Tao
AU - Ma, Yinhua
AU - Gao, Jian
AU - Feng, Lei
AU - Cui, Jingnan
AU - James, Tony D.
AU - Ma, Xiaochi
N1 - 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.
PY - 2021/11/8
Y1 - 2021/11/8
N2 - 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.
AB - 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.
KW - fluorescence imaging
KW - molecular-splicing strategy
KW - NIR fluorescent probes
KW - UDP-glucuronosyltransferase 1A1
UR - http://www.scopus.com/inward/record.url?scp=85116419803&partnerID=8YFLogxK
U2 - 10.1002/anie.202109479
DO - 10.1002/anie.202109479
M3 - Article
AN - SCOPUS:85116419803
SN - 1433-7851
VL - 60
SP - 24566
EP - 24572
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 46
ER -