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

Jing Ning; Zhenhao Tian; Jiayue Wang; Fei Yan; Chao Shi; Shujing Zhang; Lei Feng; Xiaohong Shu; Jingnan Cui; Tony D. James; Xiaochi Ma

doi:10.1002/anie.202409217

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

Jing Ning, Zhenhao Tian, Jiayue Wang, Fei Yan, Chao Shi, Shujing Zhang, Lei Feng, Xiaohong Shu, Jingnan Cui, Tony D. James, Xiaochi Ma

Research output: Contribution to journal › Article › peer-review

4 Citations (SciVal)

Abstract

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.

Original language	English
Article number	e202409217
Journal	Angewandte Chemie - International Edition
Volume	63
Issue number	41
Early online date	30 Sept 2024
DOIs	https://doi.org/10.1002/anie.202409217
Publication status	Published - 7 Oct 2024

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Acknowledgements

The authors thank the National Natural Science Foundation of China (82225048, 82174228, 82274359 and 32101202), LiaoNing Revitalization Talents Program (XLYC2203048), Dalian Medical University Interdisciplinary Research Cooperation Project Team Funding (JCHZ2023011), High-level Talents of Dalian (2023RY009) and the open Research Fund of the School of Chemistry and Chemical Engineering, Henan Normal University for support (2020ZD01 and 2021YB07) for financial support.

Keywords

analytical methods
cytochrome P450 2D6
fluorescent probes
mechanism-based inactivation
rational molecular design

ASJC Scopus subject areas

Catalysis
General Chemistry

Access to Document

10.1002/anie.202409217

Cite this

@article{ac1071be300e4d1191572263f760a460,

title = "Rational Molecular Design of a Fluorescent Probe for Selectively Sensing Human Cytochrome P450 2D6",

abstract = "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.",

keywords = "analytical methods, cytochrome P450 2D6, fluorescent probes, mechanism-based inactivation, rational molecular design",

author = "Jing Ning and Zhenhao Tian and Jiayue Wang and Fei Yan and Chao Shi and Shujing Zhang and Lei Feng and Xiaohong Shu and Jingnan Cui and James, {Tony D.} and Xiaochi Ma",

year = "2024",

month = oct,

day = "7",

doi = "10.1002/anie.202409217",

language = "English",

volume = "63",

journal = "Angewandte Chemie - International Edition",

issn = "1433-7851",

publisher = "John Wiley and Sons Inc.",

number = "41",

}

TY - JOUR

T1 - Rational Molecular Design of a Fluorescent Probe for Selectively Sensing Human Cytochrome P450 2D6

AU - Ning, Jing

AU - Tian, Zhenhao

AU - Wang, Jiayue

AU - Yan, Fei

AU - Shi, Chao

AU - Zhang, Shujing

AU - Feng, Lei

AU - Shu, Xiaohong

AU - Cui, Jingnan

AU - James, Tony D.

AU - Ma, Xiaochi

PY - 2024/10/7

Y1 - 2024/10/7

N2 - 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.

AB - 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.

KW - analytical methods

KW - cytochrome P450 2D6

KW - fluorescent probes

KW - mechanism-based inactivation

KW - rational molecular design

UR - http://www.scopus.com/inward/record.url?scp=85205380215&partnerID=8YFLogxK

U2 - 10.1002/anie.202409217

DO - 10.1002/anie.202409217

M3 - Article

AN - SCOPUS:85205380215

SN - 1433-7851

VL - 63

JO - Angewandte Chemie - International Edition

JF - Angewandte Chemie - International Edition

IS - 41

M1 - e202409217

ER -

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

Abstract

Data Availability Statement

Acknowledgements

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Embargoed Document

Fingerprint

Cite this