Synthesis and Macrodomain Binding of Mono-ADP-Ribosylated Peptides

Angew Chem Int Ed Engl. 2016 Aug 26;55(36):10634-8. doi: 10.1002/anie.201604058. Epub 2016 Jul 28.

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.

Keywords: ADP-ribosylation; peptides; posttranslational modifications; proteins; solid-phase synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation*
  • DNA Repair Enzymes / chemistry
  • DNA Repair Enzymes / metabolism
  • Histones / chemical synthesis*
  • Histones / chemistry
  • Histones / metabolism
  • Humans
  • Hydrolases / chemistry
  • Hydrolases / metabolism
  • Peptides / chemical synthesis*
  • Peptides / chemistry
  • Peptides / metabolism
  • Protein Binding
  • Protein Domains
  • Solid-Phase Synthesis Techniques / methods*
  • Thiolester Hydrolases / chemistry
  • Thiolester Hydrolases / metabolism
  • alpha-Defensins / chemical synthesis*
  • alpha-Defensins / chemistry
  • alpha-Defensins / metabolism
  • rhoA GTP-Binding Protein / chemical synthesis*
  • rhoA GTP-Binding Protein / chemistry
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Histones
  • MACROD2 protein, human
  • Peptides
  • alpha-Defensins
  • human neutrophil peptide 1
  • Hydrolases
  • OARD1 protein, human
  • Thiolester Hydrolases
  • rhoA GTP-Binding Protein
  • DNA Repair Enzymes