Click synthesis of ubiquitin dimer analogs to interrogate linkage-specific UBA domain bindingElectronic supplementary information (ESI) available: Additional MS data and experimental protocols. See DOI: 10.1039/c1cc15834a

A new route to the synthesis of triazole-linked ubiquitin dimers (diUbs) as structural analogs of the seven diUbs is reported. Binding studies with the Lys48-specific UBA domain of the Mud1 protein suggest that they represent functionally suitable surrogates of their native counterparts linked by an isopeptide bond. All seven ubiquitin dimers can be synthesized by a new route using click chemistry. These artificial mimics were explored in linkage-dependent protein interaction studies.