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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