The development of chemical tools to study the interplay of ubiquitination and ADPribosylation

Author(s):
Kloet, M.S.
Published
2025
Publication type
Doctoral Thesis

Abstract

UbADPr is a combination of the two post-translational modifications (PTMs) Adenosine diphosphate ribose (ADPr) and ubiquitin (Ub) covalently attached to each other. UbADPr has gained interest as key intermediate in the phosphoribosyl (PR)-ubiquitination pathway utilized by the Legionella bacterium to gain local control of the host Ub system. Furthermore, examples of mammalian enzymes forming UbADPr are emerging, highlighted by the identification of the Deltex RING E3 ligase family. Tools to study formation or signaling of UbADPr are scarce, mainly attributed to synthetic challenges associated with covalently linking and deprotecting UbADPr. This thesis focuses on the synthesis and application of UbADPr-tools.

Chemical BiologyUbiquitinADPrLegionellaChemical synthesisPost-translational modificationsActivity-based-probesCopper catalysed click chemistry
Defense date
2025-02-06
Language
English
Supervisor(s)
Neefjes, J.J.C.
Advisor(s)
Heden van Noort, G.J. van der
Committee member(s)
Vertegaal, A.C.O.; Kasteren, S.I. van; Martin, N.I.; Mulder, M.P.C.; Misra, M.
Qualification
Ph.D.
Degree granting institution
Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University, Leiden
hdl
1887/4179328
ISBN(s)
9789465066912

Funding

Sponsorship
NWO
Grant number
Vidi grant: 192011