Li Qiao-Qiao, Yang Yu-Xiu, Qv Jing-Wen, Hu Guang, Hu Yuan-Jia, Xia Zhi-Ning, Yang Feng-Qing
School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 401331, China.
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.
J Anal Methods Chem. 2018 Mar 20;2018:4707609. doi: 10.1155/2018/4707609. eCollection 2018.
Thrombin plays a vital role in blood coagulation, which is a key process involved in thrombosis by promoting platelet aggregation and converting fibrinogen to form the fibrin clot. In the receptor concept, drugs produce their therapeutic effects via interactions with the targets. Therefore, investigation of interaction between thrombin and small molecules is important to find out the potential thrombin inhibitor. In this study, affinity capillary electrophoresis (ACE) and in silico molecular docking methods were developed to study the interaction between thrombin and ten phenolic compounds (-hydroxybenzoic acid, protocatechuic acid, vanillic acid, gallic acid, catechin, epicatechin, dihydroquercetin, naringenin, apigenin, and baicalein). The ACE results showed that gallic acids and six flavonoid compounds had relative strong interactions with thrombin. In addition, the docking results indicated that all of optimal conformations of the six flavonoid compounds were positioned into the thrombin activity centre and had interaction with the HIS57 or SER195 which was the key residue to bind thrombin inhibitors such as argatroban. Herein, these six flavonoid compounds might have the potential of thrombin inhibition activity. In addition, the developed method in this study can be further applied to study the interactions of other molecules with thrombin.
凝血酶在血液凝固过程中起着至关重要的作用，血液凝固是血栓形成所涉及的关键过程，它通过促进血小板聚集以及将纤维蛋白原转化形成纤维蛋白凝块来实现。在受体概念中，药物通过与靶点相互作用产生治疗效果。因此，研究凝血酶与小分子之间的相互作用对于寻找潜在的凝血酶抑制剂至关重要。在本研究中，开发了亲和毛细管电泳（ACE）和计算机分子对接方法，以研究凝血酶与十种酚类化合物（对羟基苯甲酸、原儿茶酸、香草酸、没食子酸、儿茶素、表儿茶素、二氢槲皮素、柚皮素、芹菜素和黄芩苷）之间的相互作用。ACE结果表明，没食子酸和六种黄酮类化合物与凝血酶具有相对较强的相互作用。此外，对接结果表明，六种黄酮类化合物的所有最佳构象都位于凝血酶活性中心，并与作为结合凝血酶抑制剂如阿加曲班的关键残基的组氨酸57或丝氨酸195相互作用。在此，这六种黄酮类化合物可能具有凝血酶抑制活性的潜力。此外，本研究中开发的方法可进一步应用于研究其他分子与凝血酶的相互作用。
