A Naturally Occurring Isoform-Specific Probe for Highly Selective and Sensitive Detection of Human Cytochrome P450 3A5
文献类型：期刊论文
| 作者 | Wu, Jing-Jing1; Cao, Yun-Feng1,6; Feng, Liang1; He, Yu-Qi3; Hong, James Y.4; Dou, Tong-Yi1; Wang, Ping1; Hao, Da-Cheng5; Ge, Guang-Bo1; Yang, Ling2 |
| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2017-05-11 |
| 卷号 | 60页码:3804-3813 |
| DOI | 10.1021/acs.jmedchem.7b00001 |
| 英文摘要 | Cytochrome P450 (CYP) 3A5 characterized with polymorphic and extensive expression in multiple tissues is the most important P450 enzyme among the minor CYP3A isoforms. However, a selective and sensitive probe for CYP3A5 remains unavailable. In this study, we identified and characterized a naturally occurring lignan 12 (schisantherin E) as an isoform-specific probe for selective detection of CYP3A5 activity in complex biological samples. With thorough characterization including LC-MS and NMR, we found that 12 can be metabolized by CYP3A5 to generate a major metabolite 2-O-demethylated 12. Meanwhile, both reaction phenotyping and chemical inhibition experiments further revealed that CYP3A5 selectively catalyzed the 2-O-demethylation of 12. Specifically, the interactions between the Phe210 residue of CYP3A5 and methyl benzoate of 12 might play key roles in 12-O-demethylation, which was revealed by docking simulation and site-directed mutagenesis studies. These findings are beneficial for exploring the role of CYP3A5 in drug metabolism and pathologic process. |
| 语种 | 英语 |
| WOS记录号 | WOS:000401403100019 |
| 源URL | [http://cas-ir.dicp.ac.cn/handle/321008/152282]  |
| 专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
| 作者单位 | 1.Chinese Acad Sci, Dalian Inst Chem Phys, Dalian 116023, Peoples R China 2.Shanghai Univ Tradit Chinese Med, Shanghai 201203, Peoples R China 3.Zunyi Med Univ, Minist Educ, Key Lab Basic Pharmacol, Sch Pharm, Zunyi 563000, Guizhou, Peoples R China 4.Univ Illinois, Dept Biopharmaceut Sci, Chicago, IL 60612 USA 5.Dalian Jiaotong Univ, Sch Environm & Chem Engn, Dalian 116028, Peoples R China 6.Key Lab Liaoning Tumor Clin Metabol, Jinzhou, Liaoning, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wu, Jing-Jing,Cao, Yun-Feng,Feng, Liang,et al. A Naturally Occurring Isoform-Specific Probe for Highly Selective and Sensitive Detection of Human Cytochrome P450 3A5[J]. JOURNAL OF MEDICINAL CHEMISTRY,2017,60:3804-3813. |
| APA | Wu, Jing-Jing.,Cao, Yun-Feng.,Feng, Liang.,He, Yu-Qi.,Hong, James Y..,...&Yang, Ling.(2017).A Naturally Occurring Isoform-Specific Probe for Highly Selective and Sensitive Detection of Human Cytochrome P450 3A5.JOURNAL OF MEDICINAL CHEMISTRY,60,3804-3813. |
| MLA | Wu, Jing-Jing,et al."A Naturally Occurring Isoform-Specific Probe for Highly Selective and Sensitive Detection of Human Cytochrome P450 3A5".JOURNAL OF MEDICINAL CHEMISTRY 60(2017):3804-3813. |
入库方式： OAI收割
来源：大连化学物理研究所
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