A General Approach Towards Triazole-linked Adenosine Diphosphate Ribosylated Peptides and Proteins
 

A General Approach Towards Triazole-linked Adenosine Diphosphate Ribosylated Peptides and Proteins


Current chemistries 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 protocols. We present a general strategy to prepare ADPr peptide analogues based on a copper catalysed click reaction between an azide modified peptide and an alkyne modified ADPr counterpart. We expand the scope of this approach to proteins by preparing two ADPr Ubiquitin analogues carrying the biological relevant ?-glycosidic linkage. Biochemical validation using Legionella effector enzyme SdeA shows that clicked Ub-ADPr is well tolerated and highlights the potential of this strategy to prepare ADPr proteins.

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