Expanded Click Conjugation of Recombinant Proteins with Ubiquitin-Like Modifiers Reveals Altered Substrate Preference of SUMO2-Modified Ubc9

Wrestling with SUMO: The chemical conjugation of proteins with small ubiquitin-like modifiers (SUMO) can be achieved by a copper(I)-catalyzed cycloaddition and unnatural amino acid mutagenesis. This approach overcomes previous restrictions related to the primary sequence of proteins and coupling conditions. Moreover, biochemical data suggests that this triazole linkage presents the modifier in a proper distance and orientation relative to the target protein.