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新加坡国立大学姚少钦教授学术报告
 添加时间:2017/09/12 发布: 管理员
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报告时间:9月12日(周二)09:00
报告地点:科技创新大楼C501
报告题目:Recent advances in catalomics


Recent advances in catalomics


Abstract: Enzymes such as proteases, phosphatases and kinases catalyze virtually every cellular process and metabolic exchange. They not only are instrumental in sustaining life but also are required for its regulation and diversification. Diseases such as cancer can be caused by minor changes in enzyme activities. In addition, the unique enzymes of pathogenic organisms are ripe targets for combating infections. Consequently, nearly one-third of all current drug targets are enzymes. Many enzymes are also engaged in important protein-protein interactions (PPI) by through the so-called reader proteins, resulting in modulating of the enzymatic activities. Little, however, is understood about the physiological roles, substrate specificity, and downstream targets of the vast majority of these important proteins. A key step toward the biological characterization of enzymes as well as their reader proteins, and their adoption as drug targets, is the development of global solutions that bridge the gap in understanding these proteins and their interactions. Catalomics is a field in chemical biology in which chemical and biological tools are developed, enabling large-scale studies of enzymes and their reader proteins at the organism level.1In this presentation, I will discuss latest progress made in my laboratory in relation to drug discovery. Specifically, I will discuss our recent results in one (or more) of the following three specific areas: (1) the use of microarray-based technologies for discovery of potential drug candidates, particularly against normally undruggable targets such as phospho- and K(ac) reader proteins;2(2) “in situdrug profiling” for cell-based proteome-wide profiling and identification of on- and off-targets of bioactive compounds including FDA-approved drugs and natural products;3and (3) the use of novel methods in material chemical biology to achieve highly efficient, intracellular delivery of therapeutic agents including small molecules, genetic materials and proteins (including antibodies) with “smart” controlled release and diagnostic mechanisms.4


References

1.   Uttamchandani, M.; Lu, C.H.S.; Yao, S.Q.,Acc. Chem. Res.,2009,42, 1183-1192.

2.   (a) Na, Z.; Peng, B.; Ng, S.; Pan, S.; Lee, J.-S.; Shen, H.M.; Yao, S.Q.,Angew. Chem. Int. Ed.,2015,54, 2515-2519; (b) Peng, B.; Thorsell, A.-G.; Karlberg, T.; Schüler, H.; Yao, S.Q.,Angew. Chem. Int. Ed.,2017,56, 248-253.

3.   (a) Pan, S.; Zhang, H.; Wang, C.; Yao, S. C. L.; Yao, S. Q.,Nat. Prod. Rep.,2016,33, 612-620; (b) Wang, D.; Du, S.; Cazenave-Gassiot, A.; Ge, J.; Lee, J.-S.; Wenk, M.; Yao, S.Q.,Angew. Chem. Int. Ed.,2017,56, 5829-5833; (c) Li, Z.; Wang, D.; Li, L.; Pan, S.; Na, Z.; Tan, C.Y.J.; Yao, S.Q.,J. Am. Chem. Soc.,2014,136, 9990-9998; (d) Pan, S.; Jang, S.-Y; Wang, D.; Liew, S. S.; Li, Z.; Lee, J.-S.; Yao, S.Q.,Angew. Chem. Int. Ed.,2017, DOI: 10.1002/anie.201706076.

4.   (a) Yu, C.; Qian, L.; Uttamchandani, M.; Li, L.; Yao, S.Q.,Angew. Chem. Int. Ed.,2015,54,10574-10578; (b) Yu, C.; Qian, L.; Ge, J.; Fu, J.; Yuan, P.; Yao, S. C. L.; Yao, S. Q.,Angew. Chem. Int. Ed.,2016,55, 9272-9276; (c) Fu, J.; Yu, C.; Li, L.; Yao, S.Q.,J. Am. Chem. Soc.,2015,137, 12153-12160; (d) Yuan, P.; Mao, X.; Chong, K. C.; Fu, J.; Pan, S.; Wu, S.; Yu, C.; Yao, S.Q.,Small.,2017,13, 1700569; (e) Yuan, P.; Zhang, H.; Qian, L.; Mao, X.; Du, S.; Yu, C.; Peng, B.; Yao, S.Q.,Angew. Chem. Int. Ed.,2017, DOI: 10.1002/anie.201705578




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