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Molecular Tools for the Study of ADP‐Ribosylation: A Unified and Versatile Method to Synthesise Native Mono‐ADP‐Ribosylated Peptides
Author(s) -
Voorneveld Jim,
Rack Johannes Gregor Matthias,
Gijlswijk Luke,
Meeuwenoord Nico J.,
Liu Qiang,
Overkleeft Herman S.,
Marel Gijsbert A.,
Ahel Ivan,
Filippov Dmitri V.
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202100337
Subject(s) - adp ribosylation , serine , cysteine , parp1 , threonine , biochemistry , phosphorylation , chemistry , biology , enzyme , nad+ kinase , poly adp ribose polymerase , polymerase
ADP‐ribosylation (ADPr), as a post‐translational modification, plays a crucial role in DNA‐repair, immunity and many other cellular and physiological processes. Serine is the main acceptor for ADPr in DNA damage response, whereas the physiological impact of less common ADPr‐modifications of cysteine and threonine side chains is less clear. Generally, gaining molecular insights into ADPr recognition and turn‐over is hampered by the availability of homogeneous, ADP‐ribosylated material, such as mono‐ADP‐ribosylated (MARylated) peptides. Here, a new and efficient solid‐phase strategy for the synthesis of Ser‐, Thr‐ and Cys‐MARylated peptides is described. ADP‐ribosylated cysteine, apart from being a native post‐translational modification in its own right, proved to be suitable as a stabile bioisostere for ADP‐ribosylated serine making it a useful tool to further biochemical research on serine ADP‐ribosylation. In addition, it was discovered that the Streptococcus pyogenes encoded protein, Spy MacroD, acts as a Cys‐(ADP‐ribosyl) hydrolase.