A practical strategy to design and develop an isoform-specific fluorescent probe for a target enzyme: CYP1A1 as a case study
文献类型：期刊论文
| 作者 | Ge, Guang-Bo1,3; Dai, Zi-Ru1,2; Feng, Lei3; Jin, Qiang1,2; Cheng, Hailing4; Li, Yan1; Ning, Jing1; Yu, Yang1; Cui, Jing-Nan3; Yang, Ling1 |
| 刊名 | CHEMICAL SCIENCE
 |
| 出版日期 | 2017 |
| 卷号 | 8期号:4页码:2795-2803 |
| ISSN号 | 2041-6520 |
| DOI | 10.1039/c6sc03970g |
| 文献子类 | Article |
| 英文摘要 | The development of isoform-specific probe(s) for a target enzyme with multiple homologs is always challenging. Herein, a practical strategy was used to design and develop an isoform-specific probe for CYP1A1, a key cytochrome P450 isoenzyme involved in xenobiotic metabolism and bioactivation. On the basis of the subtle differences in 3D structure and substrate preference between CYP1A1 and its homolog CYP1A2, we proposed that it was possible to design a CYP1A1-specific probe via local modification of the reaction site on known CYP1A substrates. To validate this hypothesis, 4-hydroxy-1,8-naphthalimide (HN) was selected as the basic fluorophore due to its excellent optical properties, while a series of O-alkylated HN derivatives were prepared to evaluate their specificity towards CYP1A1. Our results revealed that the introduction of a chloroethyl to HN could get the best isoform selectivity towards CYP1A1 over other CYPs including CYP1A2. The newly developed probe NBCeN exhibited excellent specificity, high sensitivity, and a ratiometric fluorescence response following CYP1A1-catalyzed O-dechloroethylation. NBCeN was successfully used to real-time monitor the activity of CYP1A1 in complex biological samples and to rapidly screen CYP1A1 modulators in living systems. NBCeN could also be used for two-photon imaging of intracellular CYP1A1 in living cells and tissues with high ratiometric imaging resolution and deep tissue penetration. All these findings demonstrated that local modification of non-specific substrates was a practical strategy to develop an isoform-specific probe for a target isoenzyme, while NBCeN could serve as a specific imaging tool to explore the biological functions of CYP1A1 in complex biological systems. |
| WOS关键词 | POLYCYCLIC AROMATIC-HYDROCARBONS ; HUMAN CYTOCHROME-P450 1A2 ; HUMAN CARBOXYLESTERASE 1 ; MESSENGER-RNA LEVELS ; XENOBIOTIC METABOLISM ; HUMAN HEPATOCYTES ; HUMAN PROTEOME ; LIVING CELLS ; HUMAN LIVER ; HUMAN LUNG |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000397560500037 |
| 出版者 | ROYAL SOC CHEMISTRY |
| 源URL | [http://cas-ir.dicp.ac.cn/handle/321008/169382]  |
| 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 |
| 通讯作者 | Ge, Guang-Bo; Yang, Ling |
| 作者单位 | 1.Chinese Acad Sci, Dalian Inst Chem Phys, Dalian, Peoples R China 2.Chinese Acad Sci, Grad Sch, Beijing, Peoples R China 3.Dalian Univ Technol, State Key Lab Fine Chem, Dalian, Peoples R China 4.Dalian Med Univ, Hosp 2, Inst Canc, Dalian, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ge, Guang-Bo,Dai, Zi-Ru,Feng, Lei,et al. A practical strategy to design and develop an isoform-specific fluorescent probe for a target enzyme: CYP1A1 as a case study[J]. CHEMICAL SCIENCE,2017,8(4):2795-2803. |
| APA | Ge, Guang-Bo.,Dai, Zi-Ru.,Feng, Lei.,Jin, Qiang.,Cheng, Hailing.,...&Yang, Ling.(2017).A practical strategy to design and develop an isoform-specific fluorescent probe for a target enzyme: CYP1A1 as a case study.CHEMICAL SCIENCE,8(4),2795-2803. |
| MLA | Ge, Guang-Bo,et al."A practical strategy to design and develop an isoform-specific fluorescent probe for a target enzyme: CYP1A1 as a case study".CHEMICAL SCIENCE 8.4(2017):2795-2803. |
入库方式： OAI收割
来源：大连化学物理研究所
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