A Practical and High-Affinity Fluorescent Probe for Uridine Diphosphate Glucuronosyltransferase 1A1: A Good Surrogate for Bilirubin
文献类型：期刊论文
| 作者 | Lv, Xia1,2,3; Feng, Lei4,5; Ai, Chun-Zhi2; Hou, Jie4,5; Wang, Ping2,3; Zou, Li-Wei2,3; Cheng, Jie6; Ge, Guang-Bo2,3; Cui, Jing-Nan5; Yang, Ling3 |
| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2017-12-14 |
| 卷号 | 60期号:23页码:9664-9675 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/acs.jmedchem.7b01097 |
| 文献子类 | Article |
| 英文摘要 | This study aimed to develop a practical and high-affinity fluorescent probe for uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1), a key conjugative enzyme responsible for the elimination and detoxification of many potentially harmful compounds. Several substrates derived from N-butyl-4-phenyl-1,8-naphthalimide were designed and synthesized on the basis of the substrate preference of UGT1A1 and the principle of photoinduced electron transfer (PET). Following the preliminary screening, substrate 2 was found with a high specificity and high affinity toward UGT1A1, while such biotransformation brought remarkable changes in fluorescence emission. Both inhibition kinetic analyses and molecular docking simulations demonstrated that 2 could bind on UGT1A1 at the same ligand-binding site as bilirubin. Furthermore, this newly developed probe was successfully used for sensing UGT1A1 activities and the high-throughput screening of UGT1A1 modulators in complex biological samples. In conclusion, a practical and high-affinity fluorescent probe for UGT1A1 was designed and well-characterized, which could serve as a good surrogate for bilirubin to investigate UGT1A1-ligand interactions. |
| WOS关键词 | HUMAN UDP-GLUCURONOSYLTRANSFERASES ; DRUG-INTERACTIONS ; IN-VITRO ; FUNCTIONAL IMPLICATIONS ; HUMAN CARBOXYLESTERASES ; NATURAL INHIBITORS ; MASS-SPECTROMETRY ; SELECTIVE PROBE ; ACTIVE-SITES ; UGT1A1 |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | AMER CHEMICAL SOC |
| WOS记录号 | WOS:000418393100018 |
| 源URL | [http://cas-ir.dicp.ac.cn/handle/321008/168390]  |
| 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.Dalian Minzu Univ, Coll Life Sci, Dalian 116600, Peoples R China 2.Chinese Acad Sci, Dalian Inst Chem Phys, Dalian 116023, Peoples R China 3.Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Med, Shanghai 201203, Peoples R China 4.Dalian Med Univ, Dalian 116044, Peoples R China 5.Dalian Univ Technol, State Key Lab Fine Chem, Dalian 116024, Peoples R China 6.US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA |
| 推荐引用方式 GB/T 7714 | Lv, Xia,Feng, Lei,Ai, Chun-Zhi,et al. A Practical and High-Affinity Fluorescent Probe for Uridine Diphosphate Glucuronosyltransferase 1A1: A Good Surrogate for Bilirubin[J]. JOURNAL OF MEDICINAL CHEMISTRY,2017,60(23):9664-9675. |
| APA | Lv, Xia.,Feng, Lei.,Ai, Chun-Zhi.,Hou, Jie.,Wang, Ping.,...&Yang, Ling.(2017).A Practical and High-Affinity Fluorescent Probe for Uridine Diphosphate Glucuronosyltransferase 1A1: A Good Surrogate for Bilirubin.JOURNAL OF MEDICINAL CHEMISTRY,60(23),9664-9675. |
| MLA | Lv, Xia,et al."A Practical and High-Affinity Fluorescent Probe for Uridine Diphosphate Glucuronosyltransferase 1A1: A Good Surrogate for Bilirubin".JOURNAL OF MEDICINAL CHEMISTRY 60.23(2017):9664-9675. |
入库方式： OAI收割
来源：大连化学物理研究所
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