李超^1,2,3, 李妍^1,2,3, 李祥乾^1,2, 史大永^1,2,3
1.中国科学院 实验海洋生物学重点实验室 中国科学院 海洋研究所, 山东 青岛 266071;2.海洋药物与生物制品功能实验室, 青岛海洋科学与技术国家实验室, 山东 青岛 266235;3.中国科学院大学, 北京 100049

摘要:
二型糖尿病是一种代谢性疾病，对人类健康造成了极大的威胁。蛋白酪氨酸磷酸酶1B（PTP1B）是胰岛素信号通路中的负调控蛋白酶，是二型糖尿病治疗的重要研究靶点。本文利用酶动力学实验和分子互作技术检测了溴酚衍生物LXQ-5的PTP1B抑制作用类型和体外特异性结合作用的特点。测定糖尿病小鼠口服给药后的空腹血糖水平和血清中糖化血红蛋白以及糖化血清蛋白水平等糖尿病相关指标的变化，研究了化合物LXQ-5在小鼠体内的降糖活性。实验结果表明，LXQ-5是PTP1B的一种非竞争性抑制剂，且在体外能够与PTP1B特异性结合。LXQ-5在糖尿病小鼠体内能显著的降低空腹血糖水平和血清中糖化血红蛋白、糖化血清蛋白含量，在新型降糖药物的研发方面具有重要的研究价值。
关键词:二型糖尿病蛋白酪氨酸磷酸酶1B溴酚衍生物LXQ-5降糖活性
DOI：10.11759/hykx20190313002
分类号:R96
基金项目:国家自然科学基金（No.81773586，81703354）；中国科学院前沿科学重点研究计划（QYZDB-SSW-DQC014）

Study of PTP1B-binding activity and in vivo hypoglycemic effect of marine bromophenol derivative LXQ-5
LI Chao^1,2,3, LI Yan^1,2,3, LI Xiang-qian^1,2, SHI Da-yong^1,2,3
1.Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China;2.Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266235, China;3.University of Chinese Academy of Sciences, Beijing 100049, China
Abstract:
Type 2 diabetes mellitus is a metabolic disease that poses a great threat to human health. Protein tyrosine phosphatase 1B (PTP1B) is a negative regulatory protease in the insulin signaling pathway and an important research target in the treatment of type 2 diabetes. In this study, enzyme kinetics experiments and molecular interaction techniques were used to determine the inhibition type and the binding characteristics of the bromophenol derivative LXQ-5 and PTP1B. The hypoglycemic activity of LXQ-5 was also evaluated in diabetic mice, including the levels of fasting blood glucose, glycosylated hemoglobin, and glycosylated serum albumin. Results showed that LXQ-5 is a noncompetitive inhibitor of PTP1B and capable of specifically binding to PTP1B in vitro. LXQ-5 also significantly reduced the levels of fasting blood glucose and serum glycated hemoglobin in diabetic mice. Thus, bromophenol derivatives have great research value in the development of novel hypoglycemic drugs.
Key words:Type 2 diabetes mellitusProtein tyrosine phosphatase 1BBromophenol derivativeLXQ-5Hypoglycemic effect





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