2. Academic Validation
  3. A Practical and High-Affinity Fluorescent Probe for Uridine Diphosphate Glucuronosyltransferase 1A1: A Good Surrogate for Bilirubin

A Practical and High-Affinity Fluorescent Probe for Uridine Diphosphate Glucuronosyltransferase 1A1: A Good Surrogate for Bilirubin

  • J Med Chem. 2017 Dec 14;60(23):9664-9675. doi: 10.1021/acs.jmedchem.7b01097.
Xia Lv 1 2 3,  Lei Feng 4 5,  Chun-Zhi Ai 3,  Jie Hou 4 5,  Ping Wang 1 3,  Li-Wei Zou 1 3,  Jie Cheng 6,  Guang-Bo Ge 1 3,  Jing-Nan Cui 5,  Ling Yang 1
Affiliations

Affiliations

  • 1 Institute of Interdisciplinary Medicine, Shanghai University of Traditional Chinese Medicine , Shanghai 201203, China.
  • 2 College of Life Science, Dalian Minzu University , Dalian 116600, China.
  • 3 Dalian Institute of Chemical Physics, Chinese Academy of Sciences , Dalian 116023, China.
  • 4 Dalian Medical University , Dalian 116044, China.
  • 5 State Key Laboratory of Fine Chemicals, Dalian University of Technology , Dalian 116024, China.
  • 6 Center for Drug Evaluation and Research, Food and Drug Administration , Silver Spring, Maryland 20903, United States.
PMID: 29125289 DOI: 10.1021/acs.jmedchem.7b01097
Abstract

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.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z