1. Palladium-Triggered Chemical Rescue of Intracellular Proteins via Genetically Encoded Allene-Caged Tyrosine
- Author
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Xin Wang, Jie Li, Jiaofeng Li, Siqi Zheng, Gong Zhang, Zhi Lin, Peng Chen, Zhaoyue Zhang, Yanjun Liu, and Jie Wang
- Subjects
Stereochemistry ,Bacterial Toxins ,Lysine ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Catalysis ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Humans ,Moiety ,Taq Polymerase ,Tyrosine ,chemistry.chemical_classification ,Antigens, Bacterial ,010405 organic chemistry ,HEK 293 cells ,General Chemistry ,0104 chemical sciences ,Alkadienes ,HEK293 Cells ,Enzyme ,chemistry ,Bioorthogonal chemistry ,Palladium ,Taq polymerase ,Proto-oncogene tyrosine-protein kinase Src - Abstract
Chemical de-caging has emerged as an attractive strategy for gain-of-function study of proteins via small-molecule reagents. The previously reported chemical de-caging reactions have been largely centered on liberating the side chain of lysine on a given protein. Herein, we developed an allene-based caging moiety and the corresponding palladium de-caging reagents for chemical rescue of tyrosine (Tyr) activity on intracellular proteins. This bioorthogonal de-caging pair has been successfully applied to unmask enzymatic Tyr sites (e.g., Y671 on Taq polymerase and Y728 on Anthrax lethal factor) as well as the post-translational Tyr modification site (Y416 on Src kinase) in vitro and in living cells. Our strategy provides a general platform for chemical rescue of Tyr-dependent protein activity inside cells.
- Published
- 2016