Enzymatic Site‐Specific Functionalization of Protein Methyltransferase Substrates with Alkynes for Click Labeling

Pass and click: Protein methylation is an important posttranslational modification. Because the methyl group is a poor reporter group, new methods are needed to analyze methyltransferase substrates. A S-adenosyl-L-methionine-based cofactor was synthesized and used for the site-specific functionalization of proteins with alkynes by methyltransferases (first step) and subsequent labeling through CuAAC click chemistry (second step; see scheme).