Target Enzyme‐Activated Two‐Photon Fluorescent Probes: A Case Study of CYP3A4 Using a Two‐Dimensional Design Strategy |
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| Authors: | Dr Jing Ning Prof Wei Wang Prof Guangbo Ge Peng Chu Feida Long Prof Yongliang Yang Yulin Peng Dr Lei Feng Prof Xiaochi Ma Prof Tony D James |
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| Institution: | 1. College of Integrative Medicine, The National & Local Joint Engineering Research Center for Drug Development of Neurodegenerative Disease, College of Pharmacy, Dalian Medical University, Dalian, 116044 China;2. School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208 China;3. Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203 China;4. Center for Molecular Medicine, School of Life Science and Biotechnology, State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, 116024 China;5. Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004 China;6. Department of Chemistry, University of Bath, Bath, BA2 7AY UK |
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| Abstract: | The rapid development of fluorescent probes for monitoring target enzymes is still a great challenge owing to the lack of efficient ways to optimize a specific fluorophore. Herein, a practical two‐dimensional strategy was designed for the development of an isoform‐specific probe for CYP3A4, a key cytochrome P450 isoform responsible for the oxidation of most clinical drugs. In first dimension of the design strategy, a potential two‐photon fluorescent substrate ( NN ) for CYP3A4 was effectively selected using ensemble‐based virtual screening. In the second dimension, various substituent groups were introduced into NN to optimize the isoform‐selectivity and reactivity. Finally, with ideal selectivity and sensitivity, NEN was successfully applied to the real‐time detection of CYP3A4 in living cells and zebrafish. These findings suggested that our strategy is practical for developing an isoform‐specific probe for a target enzyme. |
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| Keywords: | Analytische Methoden Cytochrom P450 3A4 Enzym-aktivierbare Sonden Fluoreszenzsonden Molekulares Design |
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