ADP-ribose analogues: synthetic strategy towards inhibitors for viral macrodomains: SARS-CoV-2

Rijpkema, K.J. (2026)

Doctoral Thesis

Since the global COVID-19 pandemic, the coronavirus responsible (SARS-CoV-2) has been extensively probed for promising protein targets to establish drug-based therapies. One of these protein targets, the macrodomain known as Mac1, binds the post-translational modification adenosine-diphosphate-ribose (ADP-ribose) and removes it from important immunological signalling molecules. This process, critical for the propagation of the virus, can be inhibited by introducing a molecule that binds better to Mac1 than the ADP-ribose, namely, an ADP-ribose analogue.

In his thesis titled ADP-ribose analogues the author Koen J. Rijpkema explores the different facets of the ADP-ribose molecule and the way that structurally changing these facets through synthetic organic chemistry has an influence on the binding affinity of the analogues for Mac1.

• Organic
• Synthesis
• ADP-ribose
• Mac1
• Coronavirus
• Inhibitors
• SARS-CoV-2
• COVID-19
• Analogues
• Viral
• Macrodomains
• Synthetic
• Carbohydrates
• Nucleosides
• Adenosine
• Ribose

• All authors: Rijpkema, K.J.
• Supervisor: Filippov, D.V.; Codée, J.D.C.
• Committee: Ubbink, M.; Overkleeft, H.S.; Maarseveen, J.H. van; Minnaard, A.J.; Bonger, K.M.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden Institute of Chemistry (LIC), Faculty of Science, Leiden University
• Date: 2026-04-16
• DOI: doi:10.60602/1887-4302122