期刊
ACS CHEMICAL BIOLOGY
卷 14, 期 6, 页码 1102-1109出版社
AMER CHEMICAL SOC
DOI: 10.1021/acschembio.9b00102
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资金
- JSPS KAKENHI [JP16H01300, JP26460142, JP18H04536, JP17H01522, JP17K19479]
Cell biology is tightly regulated by post-translational modifications of proteins. Methods to modulate post-translational modifications in living cells without relying on enzymes or genetic manipulation are, however, largely underexplored. We previously reported that a chemical catalyst (DSH) conjugated with a nucleosome-binding ligand can activate an acyl-CoA and promote site-selective lysine acylation of histones in test tubes. In-cell acylation by this catalyst system is challenging, however, mainly due to the low cell permeability of acyl-CoA and the propensity of DSH to form inactive disulfide. Here, we report a new catalyst system effective for in-cell acylation, comprising a cell-permeable acyl donor and pro-drugged DSH. Using E. coli dihydrofolate reductase and trimethoprim as a model protein and ligand pair, the catalyst system enabled site-selective acylation of the target protein in living cells. The findings will lead to the development of useful chemical biology tools and new therapeutic strategies capable of synthetically modulating post-translational modifications.
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