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Heijden, F.L.A.M. van der (2026)

Synthetic affinity-based probes for ADP-Ribose interactome studies

Doctoral Thesis
Adenosine diphosphate ribosylation (ADP-ribosylation) is a fascinating post-translational modification (PTM) that plays a role in a variety of cellular processes and is associated with several diseases, including cancer and viral infections. To understand this PTM in more detail and consequently develop effective drugs based on this information, it is essential to investigate the key proteins involved in ADP-ribosylation: ADP-ribosyltransferases (writers), hydrolases (erasers), and the proteins interacting with ADP-ribose (readers). Much past and current research has examined proteins that function as the writers and erasers of ADP-ribosylation. This research has led to the development of anti-cancer drugs, such as olaparib, and advancements towards future antiviral therapies targeting COVID-19. However, there is also significant potential in exploring the readers of ADP-ribosylation, as they regulate many downstream processes related to ADP-ribosylated...Show moreAdenosine diphosphate ribosylation (ADP-ribosylation) is a fascinating post-translational modification (PTM) that plays a role in a variety of cellular processes and is associated with several diseases, including cancer and viral infections. To understand this PTM in more detail and consequently develop effective drugs based on this information, it is essential to investigate the key proteins involved in ADP-ribosylation: ADP-ribosyltransferases (writers), hydrolases (erasers), and the proteins interacting with ADP-ribose (readers). Much past and current research has examined proteins that function as the writers and erasers of ADP-ribosylation. This research has led to the development of anti-cancer drugs, such as olaparib, and advancements towards future antiviral therapies targeting COVID-19. However, there is also significant potential in exploring the readers of ADP-ribosylation, as they regulate many downstream processes related to ADP-ribosylated proteins and may present valuable therapeutic targets. To gain a better understanding of the readers of ADP-ribose as post-translational modification, it is essential to identify which proteins specifically interact with each of the various forms of ADP-ribose, including mono-ADP-ribose, linear poly-ADP-ribose, and branched poly-ADP-ribose. Well-defined synthetic ADP-ribose derivatives serve as ideal molecular probes in proteomics studies, allowing clear differentiation between the different forms of ADP-ribosylation. This Thesis outlines the development of novel mono- and oligo-ADP-ribose derivatives and describes their use as molecular probes in interactomics screenings to facilitate a more detailed investigation of the proteins involved in ADP-ribosylation.
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ADP-ribosylation
Synthetic probes
Bio-organic synthesis
Proteomics
All authors
Heijden, F.L.A.M. van der
Supervisor
Filippov, D.V.; Codée, J.D.C.
Committee
Ubbink, M.; Overkleeft, H.S.; Schuller, M; Vermeulen, M; Heden van Noort, G.J. van der
Qualification
Doctor (dr.)
Awarding Institution
Leiden Institute of Chemistry (LIC), Faculty of Science, Leiden University
Date
2026-03-19
DOI
doi:10.60602/1887-4297337