Molecular-splicing strategy to construct a near-infrared fluorescent probe for UDP-glucuronosyltransferase1A1.

Abstract

UDP-glucuronosyltransferase1A1 (UGT1A1) is a vital metabolic enzyme responsible for clearance of endogenous substances and drugs. Hitherto, the development of fluorescent probes for UGTs was severely restricted due to the poor isoform selectivity, 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. This practical molecular-splicing strategy is particularly powerful in developing highly selective and enzyme-activated fluorescent probes.