A General Approach Towards Triazole-Linked Adenosine Diphosphate Ribosylated Peptides and Proteins.
Qiang LiuHans A V KistemakerSagar BhogarajuIvan DikicHerman S OverkleeftGijsbert A van der MarelHuib OvaaGerbrand J van der Heden van NoortDmitri V FilippovPublished in: Angewandte Chemie (International ed. in English) (2018)
Current methods to prepare adenosine diphosphate ribosylated (ADPr) peptides are not generally applicable due to the labile nature of this post-translational modification and its incompatibility with strong acidic conditions used in standard solid-phase peptide synthesis. A general strategy is presented to prepare ADPr peptide analogues based on a copper-catalyzed click reaction between an azide-modified peptide and an alkyne-modified ADPr counterpart. The scope of this approach was expanded to proteins by preparing two ubiquitin ADPr analogues carrying the biological relevant α-glycosidic linkage. Biochemical validation using Legionella effector enzyme SdeA shows that clicked ubiquitin ADPr is well-tolerated and highlights the potential of this strategy to prepare ADPr proteins.