Synthesis and Macrodomain Binding of Mono-ADP-Ribosylated Peptides
Angew Chem Int Ed Engl. 2016 Jul 28. doi: 10.1002/anie.201604058. [Epub ahead of print]
|Authors/Editors:||Kistemaker HA, Nardozza AP, Overkleeft HS, van der Marel GA, Ladurner A, Filippov DV|
Mono-ADP-ribosylation is a dynamic posttranslational modification (PTM) with important roles in signaling. Mammalian proteins that recognize or hydrolyze mono-ADPribosylated proteins have been described. We report the synthesis of ADP-ribosylated peptides from the proteins histone H2B, RhoA and, HNP-1. An innovative procedure was applied that makes use of pre-phosphorylated amino acid building blocks. Binding assays revealed that the macrodomains of human MacroD2 and TARG1 exhibit distinct specificities for the different ADP-ribosylated peptides, thus showing that the sequence surrounding ADP-ribosylated residues affects the substrate selectivity of macrodomains.