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Synthesis and Macrodomain Binding of Mono‐ADP‐Ribosylated Peptides
Author(s) -
Kistemaker Hans A. V.,
Nardozza Aurelio Pio,
Overkleeft Herman S.,
van der Marel Gijs A.,
Ladurner Andreas G.,
Filippov Dmitri V.
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201604058
Subject(s) - rhoa , biochemistry , histone h2b , phosphorylation , peptide , peptide sequence , histone , chemistry , enzyme , plasma protein binding , microbiology and biotechnology , biology , signal transduction , gene
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.