报告题目：Recent advances in Catalomics - Perspective of Drug Discovery in Academia
报告人：Shao Q. Yao教授
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 key progress made in my laboratory in the last 18 years, in areas related to Catalomics and drug discovery in academia. Specifically, I will focus on the so-called three-Ds (Discovery, Development, and Delivery). I will start with a brief summary of our previous key results in two areas: (1) the use of microarray-based technologies for discovery of potential drug candidates, particularly against normally undruggable targets such as phospho-reader proteins;2and (2) “in situ drug profiling” for cell-based proteome-wide profiling and identification of on- and off-targets of bioactive compounds including FDA-approved drugs and natural products.3Much of my discussion will then focus on detailed accounts on (3) the use of novel methods in protein bioconjugation and material chemical biology to achieve highly efficient, intracellular delivery of therapeutic proteins including antibodies.4I will end the talk by providing a recent example of successful delivery offunctionalenzymes and antibodies to mitochondria, thesubcellularorganelles which serve as not only the powerhouse and energy provider in mammalian cells, but also the shelter for manytherapeuticallyimportant proteins.5
1.Uttamchandani, M.; Lu, C.H.S.; Yao, S.Q.,Acc. Chem. Res.,2009,42, 1183.
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; (b) Peng, B.; Thorsell, A.-G.; Karlberg, T.; Schüler, H.; Yao, S.Q.,Angew. Chem. Int. Ed.,2017,56, 248.
3.(a) Pan, S.; Zhang, H.; Wang, C.; Yao, S. C. L.; Yao, S. Q.,Nat. Prod. Rep.,2016,33, 612; (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; (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; (d) Pan, S.; Jang, S.-Y; Wang, D.; Liew, S. S.; Li, Z.; Lee, J.-S.; Yao, S.Q.,Angew. Chem. Int. Ed.,2017,56, 11816; (e) Cheng, K.; Lee, J.-S.; Yao, S.Q.; Ding, K.; Li, Z.,Angew. Chem. Int. Ed.,2017,56, 15044; (f) Pan, S.; Jang, S.-Y.; Liew, S. S.; Fu, J.; Wang, D.; Lee, J.-S.; Shao Q. Yao,Angew. Chem. Int. Ed.,2018,57, 579-583.
4.(a) Yu, C.; Qian, L.; Ge, J.; Fu, J.; Yuan, P.; Yao, S. C. L.; Yao, S. Q.,Angew. Chem. Int. Ed.,2016,55, 9272; (b) Fu, J.; Yu, C.; Li, L.; Yao, S.Q.,J. Am. Chem. Soc.,2015,137, 12153; (c) Yu, C.; Qian, L.; Uttamchandani, M.; Li, L.; Yao, S.Q.,Angew. Chem. Int. Ed.,2015,54,10574; (d) Yuan, P.; Zhang, H.; Qian, L.; Mao, X.; Du, S.; Yu, C.; Peng, B.; Yao, S.Q.,Angew. Chem. Int. Ed.,2017,56, 12481; (e) Qian, L.; Fu, J.; Yuan, P.; Du, S.; Huang, W.; Li, L.; Yao, S. Q.,Angew. Chem. Int. Ed.,2018,57, 1532; (f) Du, S.; Liew, S.S.; Li, L.; Yao, S.Q.,J. Am. Chem. Soc.2018,140, 15986; (g) Mao, X.; Yuan, P.; Yu, C.; Li L.;Yao, S.Q.,Angew. Chem. Int. Ed.2018,57, 10257.
5.Yuan, P.; Mao, X.; Wu, X.; Liew, S.S.; Li, L.; Yao, S.Q.,Angew. Chem. Int. Ed.2019,58, 7657.
Shao Q. Yao教授2001年于新加坡国立大学建立以化学生物学为研究方向的课题组，长期致力于酶及相关生物分子对生命调控的研究，以小分子荧光探针、蛋白质组学、微阵列芯片、高通量筛选等为手段，积极推进疾病的机理研究及治疗手段的开发，先后在Nature、Acc.Chem. Res., J. Am. Chem. Soc., Angew. Chem. Int. Ed., Nat. Commun., Proc. Natl. Acad. Sci. U.S.A.等国际著名期刊上发表高水平学术论文200余篇，总引用6800余次，H-index为47。至今已培养博士/硕士研究生30余名，其中有多名学生和出站博士后在国内外知名科研单位从事相关研究工作；期间也荣获诸多奖项，包括Mr & Mrs Sun Chan Memorial Award (2006),Outstanding Scientist Award(2007),ASAIHL-Scopus Young Scientist Award(2008),Asia Rising Stars Lectureship(2013)等,同时也是Angew. Chem.的International Advisory Board成员之一，并担任众多国际刊物的审稿人。