Molecular probes for human cytochrome P450 enzymes: Recent progress and future perspectives
Molecular probes for human cytochrome P450 enzymes: Recent progress and future perspectives
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人细胞色素 P450 酶的分子探针:最新进展和未来展望
DOI:
10.1016/j.ccr.2020.213600
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发表时间:
2021-01
影响因子:
20.6
通讯作者:
Guangbo Ge
中科院分区:
文献类型:
--
作者:
Jingjing Wu;Xiaoqing Guan;Ziru Dai;Rongjing He;Xinxin Ding;Ling Yang;Guangbo Ge
The cytochrome P450 enzymes (P450s or CYPs) are a class of heme-containing monooxygenases responsible for the oxidative metabolism of a wide range of endogenous substances and foreign chemicals. Deciphering the physiological functions of CYPs and their relevance to human diseases requires reliable tools for sensing target enzyme in complex biological systems. Over the past few decades, great efforts have been made to develop isoform-specific probe substrates for human CYP(s) and use them in both basic researches and translational applications. The growing database of the ligands and 3D-structures of human CYPs strongly facilitates the design and development of CYP probe substrates with improved specificity. Herein, we summarize the recent progress in the development and applications of molecular probes for human CYPs. The structural and catalytic features of human CYPs, as well as the design principles and strategies used in the development of CYP probe substrates, have been well summarized. Two comprehensive lists of molecular probes for various human CYP enzymes, including non-optical and optical probe substrates, along with their structural information and kinetic parameters, are presented. Finally, the current challenges and future perspectives in this field are proposed and highlighted. The information and knowledge presented here provides practical tools for sensing CYP activities in complex biological systems, exploring the relevance of CYPs to human diseases, as well as screening and characterizing of CYP modulators.
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作者:
Schönknecht, P;Lütjohann, D;Schröder, J
通讯作者:
Schröder, J