The development of molecular tools for investigating NAD+ metabolism and signalling

Minnee, H. (2024)

Doctoral Thesis

Nicotinamide adenine dinucleotide (NAD+) is the substrate used for the introduction of the ubiquitous and highly dynamic PTM in which either one or multiple adenosine diphosphate ribose (ADPr) moieties are covalently attached to a nucleophilic side chain of an specific amino acid in the target protein to regulate cellular pathways including adipogenesis, DNA damage repair and gene expression. A significant fraction of the nucleophilic amino acid functionalities, most recently histidine and tyrosine, have been identified as ADPr-acceptor sites. In this thesis, new methodologies have been developed to synthesize peptide fragments carrying an ADPr modification to investigate ADP-ribosylation on histidine.

• ADP-ribosylation
• Histidine
• Carba-ribose
• Cyclic sulfate
• RuAAC and CuAAC

• All authors: Minnee, H.
• Supervisor: Filippov, D.V.; Codée, J.D.C.
• Committee: Ubbink, M.; Overkleeft, H.S.; Maarseveen, J. van; Ahel, I.; Artola Perez de Azanza, M.E.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden Institute of Chemistry (LIC), Faculty of Science, Leiden University
• Date: 2024-05-23
• ISBN (print): 9789464839852