Bioorthogonal Chemical Activation of Kinases in Living Systems.
Selective manipulation of protein kinases under living conditions is highly desirable yet extremely challenging, particularly in a gain-of-function fashion. Here we employ our recently developed bioorthogonal cleavage reaction as a general strategy for intracellular activation of individual kinases. Site-specific incorporation of trans-cyclooctene-caged lysine in place of the conserved catalytic lysine, in conjunction with the cleavage partner dimethyl-tetrazine, allowed efficient lysine decaging with the kinase activity chemically rescued in living systems.
Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China; Peking-Tsinghua Center for Life Sciences, Beijing, China.
Gong
G
Zhang
Beijing National Laboratory for Molecular Sciences, Synthetic and Functional Biomolecules Center, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University , Beijing, China.
Jie
J
Li
Beijing National Laboratory for Molecular Sciences, Synthetic and Functional Biomolecules Center, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University , Beijing, China.
Ran
R
Xie
Beijing National Laboratory for Molecular Sciences, Synthetic and Functional Biomolecules Center, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University , Beijing, China.
Xinyuan
X
Fan
Beijing National Laboratory for Molecular Sciences, Synthetic and Functional Biomolecules Center, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University , Beijing, China.
Yanjun
Y
Liu
Beijing National Laboratory for Molecular Sciences, Synthetic and Functional Biomolecules Center, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University , Beijing, China.
Siqi
S
Zheng
Beijing National Laboratory for Molecular Sciences, Synthetic and Functional Biomolecules Center, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University , Beijing, China.
Yun
Y
Ge
Beijing National Laboratory for Molecular Sciences, Synthetic and Functional Biomolecules Center, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University, Beijing, China; Peking-Tsinghua Center for Life Sciences, Beijing, China.
Peng R
PR
Chen