Synthesis and Macrodomain Binding of Mono-ADP-Ribosylated Peptides

Kistemaker, Hans A. V.; Nardozza, Aurelio Pio; Overkleeft, Herman S.; Marel, Gijs A. van der; Ladurner, Andreas G. und Filippov, Dmitri V. (2016): Synthesis and Macrodomain Binding of Mono-ADP-Ribosylated Peptides. In: Angewandte Chemie-international Edition, Bd. 55, Nr. 36: S. 10634-10638

Abstract

Mono-ADP-ribosylation is a dynamic posttranslational modification (PTM) with important roles in signaling. Mammalian proteins that recognize or hydrolyze mono-ADP-ribosylated 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1433-7851
• Sprache: Englisch