Bioorthogonal Cleavage Reactions in Space and Time: From Living Cells to Living Animals
Employing small molecules or chemical reagents 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 developed bioorthogonal cleavage reactions to control protein activation in living systems with high spatial and/or temporal resolution. These reactions exhibited high efficiency and low toxicity for chemical decaging of the masked-lysine residue on intracellular proteins, which is complementary to the previously used photo-decaging reactions. We are currently employing this method to block specific kinase’s activity in living cells, which allowed the subsequent gain-of-function study of individual kinase within the intracellular signaling transduction network. Our efforts on exploring the therapeutic potential of these novel reactions for pro-drug activation will also be discussed.
AffiliationsCollege of Chemistry, Peking University, China
1. Zhao J, Liu Y, Lin F, Wang W, Yang S, Ge Y, Chen P. Bioorthogonal Engineering of Bacterial Effectors for Spatial–Temporal Modulation of Cell Signaling, ACS Cent. Sci., 2019, 5, 145-53
2. Li J, Chen P. Development and application of bond-cleavage reactions in bioorthogonal chemistry, Nat. Chem. Biol., 2016, 12, 129-37
3. Zhang G, Li J, Xie R, Fan X, Liu Y, Zheng S, Ge Y, Chen P. Bioorthogonal chemical activation of kinases in living systems, ACS Cent. Sci. 2016, 2, 325-31
4. Wang J, Zheng S, Liu Y, Zhang Z, Lin Z, Li J, Zhang G, Wang X, Li J, Chen P. Palladium-triggered chemical rescue of intracellular proteins via genetically encoded allene-caged tyrosine, J. Am. Chem. Soc. 2016, 138, 15118-21
5. Li J, Jia S, Chen P. Diels-Alder reaction-triggered bioorthogonal protein activation in living cells, Nat. Chem. Biol., 2014, 10, 1003-5
6. Li J, Yu J, Zhao J , Wang J, Zheng S, Lin S, Chen L, Yang M, Jia S, Zhang X, Chen P. Palladium-triggered deprotection chemistry for protein activation in living cells, Nat. Chem. 2014, 6, 352-61
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 as an Investigator at Peking University in July 2009 and has been promoted to Full Professor with tenure in 2014. 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 creation of versatile genetically encoded photocrosslinkers for studying protein-protein interactions, as well as the development of bioorthogonal cleavage reactions for protein activation in living systems. He received many awards including NSFC Distinguished Young Scholar Award (2012), RSC Chemical Society Review Emerging Investigator lectureship (2014), The Chemical Society of Japan Distinguished Lectureship Award (2015), 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).