2021
DOI: 10.1002/anie.202113191
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Rational Design of a Two‐Photon Fluorescent Probe for Human Cytochrome P450 3A and the Visualization of Mechanism‐Based Inactivation

Abstract: Mechanism-based inactivation (MBI) can mediate adverse reactions and hepatotoxicity from drugs, which is a result of their conversion into highly reactive metabolites catalyzed by enzymes such as cytochrome P450 3A (CYP3A). In the present research, we optimized the key interaction domain of the fluorophore with the target protein to develop a two-photon fluorescent probe for CYP3A that is involved in the metabolism of more than half of all clinical drugs. The developed BN-1 probe exhibited appropriate selecti… Show more

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Cited by 22 publications
(6 citation statements)
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“…36,39 Consequently, the detection of these enzymes using uorogenic agents has become a signicant area of interest. 40 However, the development of uorescent probes for CYPs encounters a major obstacle due to the homologous protein structure, resulting in similarities in catalytic activity and uorescence emission spectra among various CYP isoforms. Despite this challenge, several probes have been successfully designed for the substrate-specic detection of different CYP450 isoforms.…”
Section: Chemosensors Responsive To Cytochrome P450mentioning
confidence: 99%
“…36,39 Consequently, the detection of these enzymes using uorogenic agents has become a signicant area of interest. 40 However, the development of uorescent probes for CYPs encounters a major obstacle due to the homologous protein structure, resulting in similarities in catalytic activity and uorescence emission spectra among various CYP isoforms. Despite this challenge, several probes have been successfully designed for the substrate-specic detection of different CYP450 isoforms.…”
Section: Chemosensors Responsive To Cytochrome P450mentioning
confidence: 99%
“…In addition to the identification of inhibitors from drugs, DDAM was applied to the discovery the effective constitutes from herbal medicines using chromatographic-activity analysis. As shown in In addition, parts of the molecules are metabolized by human CYPs to generate chemically reactive intermediate(s) that may bind to a range of biological macromolecules covalently, resulting in protein dysfunction and/or other unexpected effects, such as idiosyncratic toxicity (Hollenberg et al, 2008;He and Feng, 2015;Gu et al, 2022) from clinical drugs and herbal medicines (Ning et al, 2022).…”
Section: Screening Of Cyp Inhibitors Using Optical Substratesmentioning
confidence: 99%
“…[18][19][20][21][22] For several decades, the uorescent probe technique has been widely used in many scientic areas [23][24][25] taking advantage of ease of operation, high sensitivity, real-time detection and in vivo imaging. [26][27][28] Fluorescent probes for imaging reactive molecules or events in living organisms could be divided into two categories: organic small molecules and nanomaterials. Compared with organic small molecules, nanoprobes have higher uorescence quantum yields, longer uorescence lifetimes, better photostability, deeper tissue penetration, and longer retention times in vivo.…”
Section: Introductionmentioning
confidence: 99%