Rational Molecular Design of a Fluorescent Probe for Selectively Sensing Human Cytochrome P450 2D6.

Autor: Ning J; The Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, China.; College of Integrative Medicine, College of Pharmacy, Dalian Medical University, Dalian, 116044, China., Tian Z; School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, China., Wang J; The Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, China.; Beijing DP Technology Co., Ltd., Beijing, 100080, China., Yan F; The Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, China., Shi C; College of Integrative Medicine, College of Pharmacy, Dalian Medical University, Dalian, 116044, China., Zhang S; The Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, China., Feng L; The Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, China.; School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, 453007, China., Shu X; College of Integrative Medicine, College of Pharmacy, Dalian Medical University, Dalian, 116044, China., Cui J; State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, 116024, China., James TD; School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, 453007, China.; Department of Chemistry, University of Bath, Bath, BA2 7AY, United Kingdom., Ma X; The Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, China.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2024 Oct 07; Vol. 63 (41), pp. e202409217. Date of Electronic Publication: 2024 Sep 06.
DOI: 10.1002/anie.202409217
Abstrakt: Cytochrome P450 2D6 (CYP2D6) is a key enzyme that mediates the metabolism of various drugs and endogenous substances in humans. However, its biological role in drug-drug interactions especially mechanism-based inactivation (MBI), and various diseases remains poorly understood, owing to the lack of molecular tools suitable for selectively monitoring CYP2D6 in complex biological systems. Herein, using a tailored molecular strategy, we developed a fluorescent probe BDPM for CYP2D6. BDPM exhibits excellent specificity and imaging capability for CYP2D6, making it suitable for the real-time monitoring of endogenous CYP2D6 activity in living bio-samples. Therefore, our tailored strategy proved useful for constructing the highly selective and enzyme-activated fluorescent probes. BDPM as a molecular tool to explore the critical roles of CYP2D6 in the pathogenesis of diseases, high-throughput screening of inhibitors and intensive investigation of CYP2D6-induced MBI in natural systems.
(© 2024 Wiley-VCH GmbH.)
Databáze: MEDLINE