陶厚朝 - 上海科技大学

研究领域

Membrane proteins (MPs) are key mediators for physiologically essential cell–cell and cell–environment communications. These proteins thus have received intensive fundamental and translational research focus, as evidenced by the fact that half of the currently marketed pharmaceuticals target MPs. Our researches have mainly focused on the ligand discovery and tool development for MPs. We have designed and synthesized a plethora of tool ligands for the chemical biology and medicinal studies over a range of MPs, mainly pharmaceutically important G protein-coupled receptors (GPCRs). The boost in the structural studies of GPCRs in the past decade greatly facilitated the design of tool ligands for many purposes, including the compounds for structural biology, fluorescence labeling, nuclear magnetic resonance (NMR) and electronic microscope (EM). We also developed a series of conceptually and structurally novel detergents, which facilitated the solubilization and stabilization of MPs and innovated the biophysics and biochemical studies.

近期论文

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Yang D, Zhou Q, Labroska V, Qin S, Darbalaei S, Wu Y, Yuliantie E, Xie L, Tao H, Cheng J, Liu Q, Zhao S, Shui W, Jiang Y, Wang MW. G protein-coupled receptors: structure- and function-based drug discovery. Signal Transduct Target Ther. 2021 Jan 8;6(1):7. Chen X, Xu Y, Qu L, Wu L, Han GW, Guo Y, Wu Y, Zhou Q, Sun Q, Chu C, Yang J, Yang L, Wang Q, Yuan S, Wang L, Hu T, Tao H, Sun Y, Song Y, Hu L, Liu ZJ, Stevens RC, Zhao S, Wu D, Zhong G. Molecular Mechanism for Ligand Recognition and Subtype Selectivity of α2C Adrenergic Receptor. Cell Rep. 2019 Dec 3;29(10):2936-2943.e4. Xue D, Xu T, Wang H, Wu M, Yuan Y, Wang W, Tan Q, Zhao F, Zhou F, Hu T, Jiang Z, Liu ZJ, Zhao S, Liu D, Wüthrich K, Tao H. Disulfide-Containing Detergents (DCDs) for the Structural Biology of Membrane Proteins. Chemistry. 2019 Sep 6;25(50):11635-11640. Xu Y, Wang Y, Wang Y, Liu K, Peng Y, Yao D, Tao H, Liu H, Song G. Mutagenesis facilitated crystallization of GLP-1R. IUCrJ. 2019 Oct 17;6(Pt 6):996-1006. Xue D, Ye L, Zheng J, Wu Y, Zhang X, Xu Y, Li T, Stevens RC, Xu F, Zhuang M, Zhao S, Zhao F, Tao H. The structure-based traceless specific fluorescence labeling of the smoothened receptor. Org Biomol Chem. 2019 Jun 26;17(25):6136-6142. Xue D, Wang J, Song X, Wang W, Hu T, Ye L, Liu Y, Zhou Q, Zhou F, Jiang ZX, Liu ZJ, Tao H. A Chemical Strategy for Amphiphile Replacement in Membrane Protein Research. Langmuir. 2019 Mar 26;35(12):4319-4327. Zhou F, Ding K, Zhou Y, Liu Y, Liu X, Zhao F, Wu Y, Zhang X, Tan Q, Xu F, Tan W, Xiao Y, Zhao S, Tao H. Colocalization Strategy Unveils an Underside Binding Site in the Transmembrane Domain of Smoothened Receptor. J Med Chem. 2019 Nov 14;62(21):9983-9989. Zhang X, Zhao F, Wu Y, Yang J, Han GW, Zhao S, Ishchenko A, Ye L, Lin X, Ding K, Dharmarajan V, Griffin PR, Gati C, Nelson G, Hunter MS, Hanson MA, Cherezov V, Stevens RC, Tan W, Tao H, Xu F. Crystal structure of a multi-domain human smoothened receptor in complex with a super stabilizing ligand. Nat Commun. 2017 May 17;8:15383. Ye L, Ding K, Zhao F, Liu X, Wu Y, Liu Y, Xue D, Zhou F, Zhang X, Stevens RC, Xu F, Zhao S, Tao H. A structurally guided dissection-then-evolution strategy for ligand optimization of smoothened receptor. Medchemcomm. 2017 Apr 28;8(6):1332-1336.