摘要
α-葡萄糖苷酶是治疗2型糖尿病的重要药物靶点之一,而基于天然产物寻找先导化合物是药物开发的重要途径。研究通过酶动力学实验和分子对接初步探讨了天然黄酮山奈酚与α-葡萄糖苷酶之间的相互作用规律。结果表明,山奈酚非竞争性抑制α-葡萄糖苷酶,并呈现浓度依赖性(IC 50=91.11±1.12μM);山奈酚可逆性结合于α-葡萄糖苷酶而呈现抑制效应。山奈酚能够显著性淬灭α-葡萄糖苷酶的内置荧光,诱使酶二级结构构象发生改变。此外,分子对接分析表明,抑制剂山奈酚可结合于α-葡萄糖苷酶活性中心,氢键和疏水性相互作用对于配体α-葡萄糖苷酶复合物构象稳定性的维系有着重要作用。
Alpha-glucosidase is one of the most important targets for the treatment of type 2 diabetes mellitus,and natural products are always the productive sources of the development of drugs.In this study,enzyme kinetics assay and molecular docking were performed to preliminarily explore the interaction mechanism of the nature flavonoid kaempferol and alpha-glucosidase.As a result,kaempferol inhibited non-competitively alpha-glucosidase in a concentration-dependent manner with IC 50 of 91.11±1.12μM.Kaempferol presented the inhibition effect by reversibly binding to the enzyme.Kaempferol could distinctly quench the intrinsic fluorescence of the enzyme and induce the conformational change of secondary structure.In addition,the analysis of molecular docking showed that kaempferol could bind to the active site of alpha-glucosidase,and hydrophobic interaction and hydrogen bonds played a key role in stabilizing the conformation of the ligand-alpha-glucosidase complex.
作者
汪大伟
赵杰
唐红进
WANG Dawei;ZHAO Jie;TANG Hongjin(Pharmacy Department,The Secondary Affliated Hospital of Anhui Medical University,Hefei 230601,China;College of Biological and Chemical Engineering,Anhui Polytechnic University,Wuhu 241000,China)
出处
《安徽工程大学学报》
CAS
2020年第1期20-25,33,共7页
Journal of Anhui Polytechnic University
基金
安徽工程大学引进人才科研启动基金资助项目(2017YQQ017)
安徽工程大学国家自然科学预研基金资助项目(2019YYZR10)
安徽工程大学2019年度大学生科学研究基金资助项目(2019DZ27)。
关键词
山奈酚
Α-葡萄糖苷酶
荧光谱分析
分子对接
kaempferol
alpha-glucosidase
fluorescence spectra analysis
molecular docking
