N-Methylation of Isopeptide Bond as a Strategy to Resist Deubiquitinases


  • This work was supported by the Israel Science foundation (A.B.), the Israel Ministry of Science and Technology (M.H.-Y.), and the European Research Council grant 293438 (RUBICAN) (M.O.).


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Stable like a rock: An efficient method to generate N-methylated isopeptide bonds has been developed. The strategy was used to generate highly stable ubiquitinated peptides and proteins that are resistant to deubiquitinases (DUBs; see scheme). Thus, the behavior of several stable ubiquitin conjugates with different DUBs was studied in vitro and within a cellular environment.