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


  • We thank Xiaodong Cheng for providing the Dim-5 expression plasmid and Kerstin Glensk for technical assistance in preparing the AdoEnYn cofactor analogue. This work was supported by the RWTH Aachen University (graduate stipend to W.P.), the Canadian Institutes of Health Research (grant MOP 37854 to D.W.L.), the Deutsche Forschungsgemeinschaft (grant LU 466/13-1 to B.L. and grants WE 1453/4-1 and 4-2 to E.W.), and the Excellence Initiative of the German Federal and State Governments.


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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).

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