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A Practical and High-Affinity Fluorescent Probe for Uridine Diphosphate Glucuronosyltransferase 1A1: A Good Surrogate for Bilirubin
Lv, Xia1,2,3; Feng, Lei4,5; Ai, Chun-Zhi3; Hou, Jie4,5; Wang, Ping1,3; Zou, Li-Wei1,3; Cheng, Jie6; Ge, Guang-Bo1,3; Cui, Jing-Nan5; Yang, Ling1
Source PublicationJOURNAL OF MEDICINAL CHEMISTRY
2017-12-14
ISSN0022-2623
DOI10.1021/acs.jmedchem.7b01097
Volume60Issue:23Pages:9664-9675
Indexed BySCI
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
WOS SubjectChemistry, Medicinal
WOS Research AreaPharmacology & Pharmacy
WOS KeywordHUMAN UDP-GLUCURONOSYLTRANSFERASES ; DRUG-INTERACTIONS ; IN-VITRO ; FUNCTIONAL IMPLICATIONS ; HUMAN CARBOXYLESTERASES ; NATURAL INHIBITORS ; MASS-SPECTROMETRY ; SELECTIVE PROBE ; ACTIVE-SITES ; UGT1A1
AbstractThis 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.
Language英语
WOS IDWOS:000418393100018
PublisherAMER CHEMICAL SOC
Citation statistics
Cited Times:14[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/168391
Collection中国科学院大连化学物理研究所
Corresponding AuthorGe, Guang-Bo; Yang, Ling
Affiliation1.Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Med, Shanghai 201203, Peoples R China
2.Dalian Minzu Univ, Coll Life Sci, Dalian 116600, Peoples R China
3.Chinese Acad Sci, Dalian Inst Chem Phys, Dalian 116023, 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
Recommended Citation
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.
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