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(11.28)【院长特约学术讲座】Bioorthogonal protein activation in living systems

发布日期:2019-11-27    浏览次数:



报告题目:Bioorthogonal protein activation in living systems

:Peng Chen, Ph.D.

Professor in Chemistry, Peking University






Dr. Peng Chen is the Cheung Kong Professor and Chairman at the Department of Chemical Biology at Peking University. He obtained BS degree in Chemistry at Peking University in 2002 and Ph.D in Chemistry at The University of Chicago in 2007. After a postdoctoral training at The Scripps Research Institute, he started his independent career at Peking University since 2009. His research focuses on developing and applying novel chemistry tools to investigate protein-based interactions and activities in living cells. His lab is best known for the development of bioorthogonal cleavage reactions for protein activation in living systems. He received many awards including NSFC Distinguished Young Scholar Award (2012), Young Scientist Award from Ministry of Education in China (2016), Tan Kah Kee Young Scientist Award (2016), and Society of Biological Inorganic Chemistry Early Career Award (SBIC award, 2017). He is currently the Associate Editor of ACS Chemical Biology.


Employing small molecules or other chemical means to modulate the function of an intracellular protein of interest, particularly in a gain-of-function fashion, remains highly desired but challenging. In this talk, I will introduce a “genetically encoded chemical decaging” strategy that relies on our recently developed bioorthogonal cleavage reactions to control protein activation in living systems. These reactions exhibit high efficiency and low toxicity for decaging the chemically “masked” lysine or tyrosine residues on intracellular proteins, allowing the gain-of-function study of individual enzymes within living cells and mice. Most recently, with the assistance of computer-based design and screening, we further expanded our method from “precise decaging”of enzyme active-sites to “proximal decaging” of enzyme pockets. This new method, termed Computationally Aided and Genetically Encoded Proximal Decaging” (CAGE-prox) (CAGE-prox), showed general applicability for switching on the activity of a broad range of proteins under living conditions. I will end by showcasing exciting applications of our CAGE-prox technique on: i) constructing orthogonal and mutually exclusive kinase signaling cascades; ii) temporal caspase activation for time-resolved profiling of proteolytic events upon apoptosis; and iii) on-demand activation of bacterial effectors as potential protein prodrugs for cancer therapy.


Selected publications:

  1. 1. Wang J, Liu Y, Liu YJ, Zheng S, Wang X, Zhao J, Yang F, Zhang G, Wang C*, Chen P*. Nature, 2019, 569, 509-13.
  2. Li J, Chen P*. Nat. Chem. Biol. 2016, 12, 129-37.
  3. Wang J, Zheng S, Liu Y, Zhang Z, Lin Z, Li J, Zhang G, Wang X, Li J, Chen P*. J. Am. Chem. Soc. 2016, 138, 15118-21.
  4. Li J, Jia S, Chen P*. Nat. Chem. Biol., 2014, 10, 1003-5.
  5. Li J, Yu J, Zhao J , Wang J, Zheng S, Lin S, Chen L, Yang M, Jia S, Zhang X, Chen P *. Nat. Chem.2014,6, 352-61.