Halomethyl-Triazoles for Rapid, Site-Selective Protein Modification

Post-translational modifications (PTMs) are used by organisms to control protein structure and function after translation, but their study is complicated roles not often well understood as PTMs difficult introduce onto proteins selectively. Designing reagents that both good mimics of PTMs, also only modify select amino acid residues in challenging. Frequently, a chemical warhead linker used, creating product misrepresentation the natural modification. We have previously shown biotin-chloromethyl-triazole an effective reagent for cysteine modification give S-Lys derivatives where triazole mimic lysine acylation. Here, we demonstrate how reactivity alkylating can be increased range PTM expanded. These new iodomethyl-triazole able residue on histone with excellent selectivity 30 min acylated side-chains. Studies more complicated, folded SCP-2L showed promising reactivity, suggested halomethyl-triazoles potent alkylators methionine residues.