Synthesis and Macrodomain Binding of Mono‐ADP‐Ribosylated Peptides |
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| Authors: | Hans A. V. Kistemaker Dr. Aurelio Pio Nardozza Prof. Dr. Herman S. Overkleeft Prof. Dr. Gijs A. van der Marel Prof. Dr. Andreas G. Ladurner Dr. Dmitri V. Filippov |
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| Affiliation: | 1. http://biosyn.lic.leidenuniv.nl/;2. Leiden Institute of Chemistry, Dept. of Bio-organic Synthesis, Leiden University, Leiden, The Netherlands;3. Department of Physiological Chemistry, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-Universit?t München, Planegg-Martinsried, Germany;4. http://www.ladurnerlab.de/;5. Center for Integrated Protein Science Munich (CIPSM), Ludwig-Maximilians-Universit?t München, Munich, Germany;6. Munich Cluster for Systems Neurology (SyNergy), Ludwig-Maximilians-Universit?t München, Munich, Germany |
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| 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. |
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| Keywords: | ADP-ribosylation peptides posttranslational modifications proteins solid-phase synthesis |
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