title: Synthesis and Macrodomain Binding of Mono-ADP-Ribosylated Peptides.
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.
authors.affiliation: Leiden Institute of Chemistry, Dept. of Bio-organic Synthesis, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.
authors.forename: Hans A V
authors.initials: HA
authors.lastname: Kistemaker
authors.affiliation: Department of Physiological Chemistry, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-Universität München, Großhaderner Street 9, 82152, Planegg-Martinsried, Germany.
authors.forename: Aurelio Pio
authors.initials: AP
authors.lastname: Nardozza
authors.affiliation: Leiden Institute of Chemistry, Dept. of Bio-organic Synthesis, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.
authors.forename: Herman S
authors.initials: HS
authors.lastname: Overkleeft
authors.affiliation: Leiden Institute of Chemistry, Dept. of Bio-organic Synthesis, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.
authors.forename: Gijs A
authors.initials: GA
authors.lastname: van der Marel
authors.affiliation: Department of Physiological Chemistry, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-Universität München, Großhaderner Street 9, 82152, Planegg-Martinsried, Germany. andreas.ladurner@med.lmu.de.|Center for Integrated Protein Science Munich (CIPSM), Ludwig-Maximilians-Universität München, Butenandt Street 5, 81377, Munich, Germany. andreas.ladurner@med.lmu.de.|Munich Cluster for Systems Neurology (SyNergy), Ludwig-Maximilians-Universität München, Feodor Lynen Street 17, 81377, Munich, Germany. andreas.ladurner@med.lmu.de.
authors.forename: Andreas G
authors.initials: AG
authors.lastname: Ladurner
authors.affiliation: Leiden Institute of Chemistry, Dept. of Bio-organic Synthesis, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands. filippov@chem.leidenuniv.nl.
authors.forename: Dmitri V
authors.identifier: 0000-0002-6978-7425
authors.initials: DV
authors.lastname: Filippov
mesh_terms: D000074744:ADP-Ribosylation; D045643:DNA Repair Enzymes / Q000737:chemistry / Q000378:metabolism; D006657:Histones / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006867:Hydrolases / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D000072417:Protein Domains; D060327:Solid-Phase Synthesis Techniques / Q000379:methods*; D013869:Thiolester Hydrolases / Q000737:chemistry / Q000378:metabolism; D023084:alpha-Defensins / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism
chemical_list: D006657:Histones; C523332:MACROD2 protein, human; D010455:Peptides; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; D006867:Hydrolases; C581913:OARD1 protein, human; D013869:Thiolester Hydrolases; D020742:rhoA GTP-Binding Protein; D045643:DNA Repair Enzymes
keywords: ADP-ribosylation; peptides; posttranslational modifications; proteins; solid-phase synthesis