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.

Activity-based NIR fluorescent probes based on the versatile hemicyanine scaffold: design strategy, biomedical applications, and outlook

“…73). 76 Probe HHC was almost non-fluorescent due to splicing of the 5-OH recognition moiety with the 6-OH fluorescent site. Upon addition of UGT1A1, the glucuronidation reaction occurred at 5-OH of probe HHC , resulting in the recovery of NIR fluorescence (∼720 nm).…”

“…74,75 Intriguingly, Ma and co-workers adopted a molecular-splicing strategy to construct a novel hydroxyl hemicyanine fluorophore derivative in fluorescence-off state that could be applied to monitor phase II metabolic enzymes with a turn-on signal. 76…”

NIR‐II Fluorescent Probe for Detecting Trimethylamine Based on Intermolecular Charge Transfer

“…With the development of biomedical sciences, clinical experimental studies have proved that some small molecules in organisms are closely related to cell proliferation, differentiation and apoptosis. In addition, these small molecules may play an important role in the physiological and pathological processes of organisms [1–7] . Trimethylamine (TMA), a human intestinal microbiota metabolizes product, has attracted more and more attention of medical researchers.…”

“…In addition, these small molecules may play an important role in the physiological and pathological processes of organisms. [1][2][3][4][5][6][7] Trimethylamine (TMA), a human intestinal microbiota metabolizes product, has attracted more and more attention of medical researchers. In the liver, TMA can be further oxidized to trimethylamine oxide (TMAO), which may lead to human cardiovascular disease, chronic kidney disease, diabetes, cancer and so on.…”

Endoplasmic Reticulum-Targeting Near-Infrared Fluorescent Probe for CYP2J2 Activity and Its Imaging Application in Endoplasmic Reticulum Stress and Tumor

“…Recently, the fluorescence technology has been widely used in the phototherapy, diagnosis, visual detection, and other fields. − The advantages of fluorescent probes such as noninvasive, real-time sampling capability, and sensitive and high spatiotemporal resolution make it much more convenient for the specific assay of target enzymes. − Among various fluorophores, the near-infrared (NIR) fluorescent probes exhibited some prominent advantages owing to its excellent tissue penetration and low background fluorescence, which allowed the visual detection of some vital metabolic enzymes for in vivo imaging. − …”