Leiden University Scholarly Publications

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Voorneveld, J.; Rack, J.G.M.; Gijlswijk, L.M. van; Meeuwenoord, N.J.; Liu, Q.; Overkleeft, H.S.; ... ; Filippov, D.V. (2021)

Molecular tools for the study of ADP-Ribosylation: a unified and versatile method to synthesise native mono-ADP-ribosylated peptides

Article / Letter to editor
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...Show moreADP-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, SpyMacroD, acts as a Cys-(ADP-ribosyl) hydrolase.Show less
All authors
Voorneveld, J.; Rack, J.G.M.; Gijlswijk, L.M. van; Meeuwenoord, N.J.; Liu, Q.; Overkleeft, H.S.; Marel, G.A. van der; Ahel, I.; Filippov, D.V.
Date
2021-05-06
Journal
Chemistry-a European Journal
Volume
27
Issue
41
Pages
10621 - 10627
DOI
doi:10.1002/chem.202100337