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讲准字292号:Where is the molecular action target?

发布时间:2018-10-12|浏览次数:

题目:Where is the molecular action target?

主讲:Qing X. Li (李庆孝)

时间:2018年10月15日 14:00

地点:化学化工学院212报告厅

主办:化学化工学院


主讲简介:Qing X. Li (李庆孝),夏威夷大学马诺阿分校教授。研究专长:农用化学品和蛋白质组学。李庆孝教授,美国加州大学戴维斯分校博士,美国加州大学伯克利分校博士后,夏威夷大学马诺阿分校教授,夏威夷农药残留研究实验室主任。李庆孝教授主要研究方向为农用化学品和蛋白质组学,长期从事分子生物学研究,是酶联免疫反应在环境检测研究应用方面的权威专家,已发表SCI论文350余篇,他引5000余次。李庆孝教授是Journal of Agricultural and Food Chemistry副主编,Pesticide Biochemistry and Physiology等期刊编委。

 

主讲内容:Mechanism of action is pivotal of pharmacological studies and drug discovery. It involves identification and characterization of a specific molecular target to which the drug binds, such as an enzyme or receptor. This talk will discuss how the flavonoid isoorientin selectively inhibits glycogen synthase kinase-3β (GSK3β) in vitro. GSK3β emerges as an important therapeutic target in neurodegenerative diseases such as Alzheimer’s disease (AD). GSK3β is a key enzyme catalyzing hyperphosphorylation of tau protein. Selective inhibition of GSK3β is a promising therapeutic strategy for AD treatment. Semi-synthesis of isoorientin has led greater than 300 fold potency improvement. Enzyme kinetic studies and molecular modeling demonstrated that both isoorientin and its synthetic analogs specifically inhibit GSK3β via a substrate competitive, rather than the common ATP competitive mode. Structure-activity relationship analyses and in silico modeling suggest the mechanism of actions by which the hydrophobic, π-cation and orthogonal multipolar interactions are involved for the GSK3β inhibition and selectivity. Cellular studies further demonstrated that those flavonoids effectively attenuate GSK3β-catalyzed tau hyperphosphorylation and is neuroprotective against amyloid-induced neurotoxicity in human SH-SY5Y cells. The new inhibitors are valuable chemical probes and drug leads with therapeutic potential to tackle AD and other GSK-3β relevant diseases.


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