Li Mei, Lee Philbert, Zhang Yao, Ma ZhiYuan, Yang Feng, Zhou Zuping, Wu Xiaoyang, Liang Hong
College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, Hunan, China; State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China, Guangxi Normal University, Guilin, 541004, Guangxi, China.
Chem Biol Drug Des. 2014 Feb;83(2):167-73. doi: 10.1111/cbdd.12208. Epub 2013 Oct 4.
To investigate the interactions between natural drugs and human serum albumin (HSA), we performed fluorescence spectroscopy and X-ray crystallography to gain insight into binding mechanism and behaviour of rhein to HSA. Our fluorescence results demonstrated that rhein strongly binds with HSA, and other compounds may affect binding affinity of rhein to different extent. Structural analysis revealed that rhein binds to the IIA subdomain of HSA. The carboxylate group of rhein forms hydrogen bonds with Arg218 and Lys199, as well as a salt bond with Arg222. Hydroxyl group (4) of rhein forms a hydrogen bond with His242, and hydroxyl group (5) of rhein forms a hydrogen bond with Arg257. Oxygen atom (7) of rhein forms a hydrogen bond with Arg222, and oxygen atom (6) of rhein forms a hydrogen bond with H₂O. Furthermore, hydroxyl group (4) of rhein also forms a hydrogen bond with H₂O. Our results reveal the biochemical and structural characteristics of the interaction between rhein and HSA, providing guidance for future development of rhein-based compounds and a drug-HSA delivery system.
为了研究天然药物与人血清白蛋白（HSA）之间的相互作用，我们进行了荧光光谱分析和X射线晶体学分析，以深入了解大黄酸与HSA的结合机制和行为。我们的荧光结果表明，大黄酸与HSA强烈结合，其他化合物可能在不同程度上影响大黄酸的结合亲和力。结构分析表明，大黄酸与HSA的IIA亚结构域结合。大黄酸的羧基与Arg218和Lys199形成氢键，以及与Arg222形成盐键。大黄酸的羟基（4）与His242形成氢键，大黄酸的羟基（5）与Arg257形成氢键。大黄酸的氧原子（7）与Arg222形成氢键，大黄酸的氧原子（6）与H₂O形成氢键。此外，大黄酸的羟基（4）也与H₂O形成氢键。我们的结果揭示了大黄酸与HSA相互作用的生化和结构特征，为未来基于大黄酸的化合物和药物-HSA递送系统的开发提供了指导。
