刘东祥 - 中国科学院上海药物研究所 -

研究领域

目前我们的兴趣集中在Bcl-2家族蛋白、Sirtuins和淀粉样肽，我们旨在表征这些蛋白质的结构特征、它们与配体分子（小分子化合物、肽或蛋白质）的相互作用，在此基础上，我们希望阐明这些蛋白的作用机制。此外，我们还设计新化合物，调控这些蛋白的功能，并在细胞水平和动物模型上验证这些化合物的生物活性。在我们的实验工作中，除了计算化学、常规生物化学和生物物理方法之外，我们还应用单分子荧光技术，研究单个分子在溶液和膜环境中的行为特征，获取在宏观尺度难以观察到的一些信息。

近期论文

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Wu J, Li J, Xu MH, Liu D*. Structure-activity relationship and interaction studies of new SIRT1 inhibitors with the scaffold of 3-(furan-2-yl)-[1,2,4]triazolo[3,4-b] [1,3,4]thiadiazole. Bioorg. Med. Chem. Lett. 2014 May 20. pii: S0960-894X(14)00528-9. doi: 10.1016/j.bmcl.2014.05.028. Wu J, Li Y, Chen K, Jiang H, Xu MH, Liu D*. Identification of benzofuran-3-yl(phenyl)methanones as novel SIRT1 inhibitors: binding mode, inhibitory mechanism and biological action. Eur. J. Med. Chem. 2013; 60:441-50. Wu J, Zhang D, Chen L, Li J, Wang J, Ning C, Yu N, Zhao F, Chen D, Chen X, Chen K, Jiang H, Liu H, Liu D*. Discovery and mechanism study of SIRT1 activators that promote the deacetylation of fluorophore-labeled substrate. J. Med. Chem. 2013; 56(3):761-80 Wang F, Liu D, Wang H, Luo C, Zheng M, Liu H, Zhu W, Luo X, Zhang J, Jiang H. Computational screening for active compounds targeting protein sequences: methodology and experimental validation. J. Chem. Inf. Model. 2011; 51(11):2821-8. Zhou Y, Jiang C, Zhang Y, Liang Z, Liu W, Wang L, Luo C, Zhong T, Sun Y, Zhao L, Xie X, Jiang H, Zhou N, Liu D*, Liu H*. Structural Optimization and Biological Evaluation of Substituted Bisphenol A Derivatives as Beta-Amyloid Peptide Aggregation Inhibitors. J. Med. Chem. 2010; 53(15):5449-66. Feng Y, Ding X, Chen T, Chen L, Liu F, Jia X, Luo X, Shen X, Chen K, Jiang H, Wang H*, Liu H*, Liu D*. Design, Synthesis and Interaction Study of Quinazoline- 2(1H)-Thione Derivatives as Novel Potential Bcl-xL Inhibitors. J. Med. Chem. 2010; 53:3465-79. Jiang C, Feng Y, Huang X, Xu Y, Zhang Y, Zhou N, Shen X, Chen K, Jiang H*, Liu D*. An enzyme-linked immunosorbent assay to compare the affinity of chemical compounds for Beta-Amyloid peptide as a monomer. Anal. Bioanal. Chem. 2010; 396:1745-54. Chen L, Feng Y, Zhou Y, Zhu W, Shen X, Chen K, Jiang H, Liu D*. Dual role of Zn2+ in maintaining structural integrity and suppressing deacetylase activity of SIRT1. J. Inorg. Biochem. 2010; 104(2):180-5. Feng Y, Liu D*, Shen X, Chen K, Jiang H. Structure assembly of Bcl-xL through α5-α5 and α6-α6 interhelix interactions in lipid membranes. Biochim. Biophys. Acta-Biomembranes. 2009; 1788(11):2389-95. Feng Y, Wu J, Chen L, Luo C, Shen X, Chen K, Jiang H, Liu D*. A fluorometric assay of SIRT1 deacetylation activity through quantification of nicotinamide adenine dinucleotide. Anal. Biochem. 2009; 395(2):205-10. Feng Y, Zhang L, Hu T, Shen X, Ding J, Chen K, Jiang H, Liu D*. A conserved hydrophobic core at Bcl-xL mediates its structural stability and binding affinity with BH3-domain peptide of pro-apoptotic protein. Arch. Biochem. Biophys. 2009; 484(1):46-54.