We report a novel strategy for site-specific acylation of recombinant proteins that proceeds via chemoselective azidation of cysteine residues using a vinyl thianthrenium salt and sodium azide, followed by traceless Staudinger ligation with acyl-functionalized phosphinoester reagents. The utility of this method is exemplified by the efficient preparation of a panel of site-specifically acylated ubiquitin variants and a crotonylated histone, providing a practical tool for accessing homogeneous acylated proteins to advance mechanistic studies of lysine acylation.
Cui et al. (Thu,) studied this question.