Chemical Tools to Study Protein ADP-Ribosylation

[Image: see text] Post-translational modification of substrate proteins plays crucial roles in the regulation of their activity, cellular localization, and ability to be recognized by other proteins. One of those modifications involves the installment of adenosine-diphosphate-ribose (ADPr) onto nucleophilic side-chain groups of amino acid residues. This highly dynamic process is regulated by ADP-ribosyl transferases (ARTs) that install the ADPr-molecules on selected proteins and poly(ADP-ribosyl) glycohydrolases (PARGs) and (ADP-ribosyl)hydrolases (ARHs) that trim down and remove ADPr-chains. In this mini-review, the most recent advances in the chemical synthesis of ADPr-conjugates, poly-ADP-ribose, ADPr-peptides, and -proteins, and other tools to investigate ADPr-biology are discussed.