A Pyrrolysine Analogue for Site-Specific Protein Ubiquitination


  • This research was supported by a grant from the US National Institutes of Health (GM061796) and an American Heart Association Great Rivers Affiliate Predoctoral Fellowship (0815449D) to X.L. We also thank the staff of the CCIC Mass Spectrometry and Proteomics Facility at OSU for protein analysis by mass spectrometry, Professor Michael Zhu (OSU) for providing Rattus norvegicus CaM cDNA, and Professor Bing Hao (UConn) for the human ubiquitin cDNA.


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The art of stitching proteins: D-Cys-ε-Lys and its diastereomer L-Cys-ε-Lys read through the UAG codon (see scheme). As the resulting proteins can participate in native chemical ligation (NCL), this process provides a means to prepare proteins chemoselectively modified (e.g. ubiquitinated) through a peptidic side chain located at the ε position of a rationally selected lysine residue.