报告一:
题 目：基于核酸控制的蛋白质标记、药物筛选、和靶点识别
报告人：李笑宇 特聘研究员
北京大学 化学与分子工程学院
时 间：2014年12月29日（星期一）上午9:00
地 点：唐仲英楼B501
摘要：在化员工物学和药物化学研究中，表征小分子和生物体系之间的相互作用有着重要的科学意义。一方面，当一个小分子化合物显示出生物活性时，识别与其相互作用的生物大分子靶点，是阐明其在分子层面上的作用机制，理解其调控的信号传导通路机理的关键。另一方面，利用化学多样性的分子库，对已知的靶点进行筛选，以获得新颖的小分子配体，则能够为分子探针和药物先导化合物的研究提供起点。因此，发展能够准确、高选择性、高灵敏度、以及高通量地进行小分子-蛋白质之间相互作用的研究策略和技术方法，是领域中的一个重要研究方向，有着重要的科学意义和应用前景。近年以来，基于DNA的有机合成、分子探针、分子库筛选等方面的研究逐渐兴起，在本领域的研究中，DNA 分子不仅是基因信息的载体，而已经成为一种灵活而且有效的工具，用于化学反应性的控制和化合物的标记。本报告将介绍本课题组在这一方面的三个研究实例：特拉唑嗪的靶点识别，蛋白质标记双探针技术，和基于DNA编码分子库的药物筛选。 报告二:
题 目: Chemical Tools for Probing Glycosylation Dynamics In Vivo
报告人: Professor Xing Chen
College of Chemistry and Molecular Engineering, Center for Life Sciences, Peking University, Beijing, 100871, China (email: xingchen@pku.edu.cn)
时 间：2014年12月29日（星期一）上午10:00
地 点：唐仲英楼B501
Glycosylation plays a key role in mediating molecular recognition, development, and cell signaling. Intriguingly, cellular glycans are highly dynamic in various physiological and pathological processes. Our research group works on developing chemical tools to label, visualize, and modulate glycosylation in living systems. Here, we present the development of a liposome-based strategy for cell-selective metabolic labeling of glycans and a FRET-based method for protein-specific imaging of cell-surface glycans.[1,2] Furthermore, we have applied those chemical tools to dissect the glycosylation changes during cardiac hypertrophy and tumor progression.[3,4] Finally, we are interested in developing new imaging modalities other than the more conventional fluorescence microscopy for glycan visualization. A recently developed bioorthogoal Raman imaging technique will be discussed.[5,6]
References:
01. Lin, W.; Du, Y.; Zhu, Y.; Chen, X. “A Cis-membrane FRET-based Method for Protein- specific Imaging of Cell-Surface Glycans” J. Am. Chem. Soc. 2014, 136, 679-687.
02. Xie, R.; Hong, S.; Feng, L.; Rong, J.; Chen, X. “Cell-Selective Metabolic Glycan Labeling Based on Ligand-Targeted Liposomes” J. Am. Chem. Soc. 2012, 134, 9914-9917.
03. Rong, J.; Han, J.; Dong, L.; Tan, Y.; Yang, H.; Feng, L.; Wang, Q.; Meng, R.; Zhao, J.; Wang, S.; Chen, X. “Glycan Imaging in Intact Rat Hearts and Glycoproteomic Analysis Reveal the Upregulation of Sialylation during Cardiac Hypertrophy” J. Am. Chem. Soc. 2014, DOI: 10.1021/ja508484c.
04. Xie, R.; Dong, L.; Huang, R.; Hong, S.; Lei, R.; Chen, X. “Targeted Imaging and Proteomic Analysis of Tumor-Associated Glycans in Living Animals” Angew. Chem. Int. Ed. 2014, 53, 14082-14086.
05. Lin, L.; Tian, X.; Hong, S.; Dai, P.; You, Q.; Wang, R.; Feng, L.; Xie, C.; Tian, Z.; Chen, X. “A Bioorthogonal Raman Reporter Strategy for SERS Detection of Glycans on Live Cells. Angew. Chem. Int. Ed. 2013, 52, 7266-7271.
06. Hong, S.; Chen, T.; Zhu, Y.; Li, A.; Huang, Y.; Chen, X. “Live-Cell Stimulated Raman Scattering Imaging of Alkyne-Tagged Biomolecules” Angew. Chem. Int. Ed. 2014, 53, 5827-5831. 配位化学国家重点实验室 |
