海洋溴酚衍生物LXQ-5的PTP1B的结合作用和体内降糖活性研究

Study of PTP1B-binding activity and in vivo hypoglycemic effect of marine bromophenol derivative LXQ-5

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。

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 re- search target in the treatment of type 2 diabetes. In this study, enzyme kinetics experiments and molecular interac- tion techniques were used to determine the inhibition type and the binding characteristics of the bromophenol de- rivative 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.