电喷雾-离子淌度质谱结合光谱法研究黄酮醇与胰淀素的相互作用  

Interaction Studies of Human Islet Amyloid Polypeptide and Flavonols by Electrospray Ionization-Ion Mobility-Mass Spectrometry and Fluorescence Spectroscopy

作　　者：庞博 孟鑫 边新宇 刘舒[1] 皮子凤[1] 刘志强[1] 宋凤瑞[1] PANG Bo;MENG Xin;BIAN Xin-Yu;LIU Shu;PI Zi-Feng;LIU Zhi-Qiang;SONG Feng-Rui(Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences,Changchun 130022,China;School of Applied Chemistry and Engineering,University of Science and Technology of China,Hefei 230029,China)

机构地区：[1]中国科学院长春应用化学研究所,吉林省中药化学与质谱重点实验室,长春130022 [2]中国科学技术大学应用化学与工程学院,合肥230026

出　　处：《分析化学》2021年第11期1881-1889,I0009-I0011,共12页Chinese Journal of Analytical Chemistry

基　　金：国家自然科学基金项目(No.21673219,81873193)资助。

摘　　要：利用电喷雾-离子淌度质谱结合荧光光谱法考察了5种黄酮醇类化合物(紫云英苷、异槲皮苷、异鼠李素-3-O-新橙皮糖苷、异鼠李素-3-O-芸香糖苷和芦丁)与人胰岛素淀粉样多肽(胰淀素,Human islet amyloid polypeptide,hIAPP)之间的相互作用。结果表明,黄酮醇化合物结构中的糖基和苷元上的羟基均能增加化合物与hIAPP结合的亲和性,并可提高hIAPP与黄酮醇配体结合形成的复合物在气相中的稳定性。不同黄酮醇类化合物在抑制hIAPP聚集方面的差别主要来自于苷元中多羟基结构,以及糖基数目和糖基类型不同所带来的影响。这5种黄酮醇类化合物中,芦丁与hIAPP的结合形成的复合物最稳定,并且对hIAPP聚集的抑制效果最明显。离子淌度质谱的研究结果表明,芦丁可能通过与hIAPP结合形成复合物稳定hIAPP的构象状态,从而发挥其对hIAPP聚集的抑制作用。本研究通过了解结构差异对于黄酮醇类化合物与hIAPP相互作用的影响,为从天然产物中筛选潜在的小分子抑制剂提供依据。The interaction of human islet amyloid polypeptide(hIAPP)with five kinds of flavonols(Astragalin,isoquercitrin,isorhamnetin-3-O-neohesperidoside,isorhamnetin-3-O-rutinoside,rutin)was investigated by electrospray ionization-ion mobility-mass spectrometry(ESI-IM-MS)and fluorescence spectroscopy.The results showed that the glycosyl groups and hydroxyl groups of aglycones in flavonols could improve their binding affinity with hIAPP,and enhance the gas phase stability of the complexes formed by hIAPP and ligands.However,the effects of multiple hydroxyl groups of aglycones on IAPP aggregation was more obvious,followed by the number of glycosyl groups and different types of glycosyl groups.Among the five flavonols,the complexes formed by rutin and hIAPP were the most stable and rutin had the strong inhibitory action on the fibrillation of hIAPP.IM-MS analysis results showed that rutin could stabilize the conformation of hIAPP by binding to hIAPP.The obtained results were useful to understand the structure-activity of the interaction of flavonols with hIAPP and provide valuable reference for the screening of potent amyloid inhibitors from natural products.

关 键 词：人胰岛素淀粉样多肽 黄酮醇 电喷雾-离子淌度质谱 荧光光谱 相互作用 

分 类 号：TQ460.1[化学工程—制药化工] O657[理学—分析化学]