Stereoretentive Post-Translational Protein Editing

Chemical post-translational methods now allow convergent side-chain editing of proteins as a form of direct chemical mutagenesis without needing to resort to genetic intervention. Current approaches that allow the creation of constitutionally native side-chains via C–C formation using off-protein carbon-centred C• radicals added to unnatural amino acid radical acceptor SOMOphile ‘tags’ such as dehydroalanine are benign and wide-ranging. However, they also typically create epimeric mixtures of D-/L-residues. Here we describe a light-mediated desulfurative method that, through the creation and reaction of stereoretained on-protein L-alanyl Cβ• radicals, allows Cβ–Hγ, Cβ–Oγ, Cβ–Seγ, Cβ–Bγ and Cβ–Cγ bond formation to flexibly generate site-selectively edited proteins with full retention of native stereochemistry under mild conditions from a natural amino acid. This methodology shows great potential to explore protein side-chain diversity and construct useful bioconjugates. This dataset contains LCMS data of tryptic digests of a PstS protein selectively modified by different radical acceptors (modification site D178). In total, 16 LCMS files are presented along with the results of the identification by MSFragger, corresponding to the variants of the PstS protein with different modifications.