Affinity-based profiling of the adenosine receptors

Beerkens, B.L.H. (2023)

Doctoral Thesis

The adenosine receptors are proteins that reside in the extracellular membranes of cells. Activation of adenosine receptors plays a role in many physiological and pathological processes, such as immune responses and cancers. Binding the adenosine receptors by either agonists or antagonists is therefore an interesting strategy currently carried out in multiple drug discovery programs. In order to make such drug discovery programs successful, our general understanding of adenosine receptor functioning should be improved. In that sense, new molecular tools can aid studies towards the adenosine receptors, for example by aiding the detection of receptor proteins or deciphering activation pathways. In this thesis, the development (synthesis, pharmacological evaluation and biological application) of chemical probes as molecular tool compounds for the adenosine receptors is described. This comprises the development of a covalent ligand for the adenosine A2B receptor, affinity-based probes for the adenosine A1 and A3 receptors and a ligand-directed probe for the adenosine A2B receptor. These chemical probes will aid future studies towards the roles of the A2B, A1 and A3 receptors in various conditions.

• G Protein-Coupled Receptors (GPCRs)
• Chemical Biology'
• Medicinal Chemistry
• Affinity-Based Probes
• Fluorescent Probes
• Covalent Ligands
• Ligand-Directed Chemistry
• Membrane Proteins
• Small Molecules
• Drug Discovery

• All authors: Beerkens, B.L.H.
• Supervisor: Ijzerman, A.P.
• Co-supervisor: Es, D. van der
• Committee: Irth, H.; Lange, E.C.M. de; Stelt, M. van der; Jacobson, K.A.; Bonger, K.M.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden Academic Centre for Drug Research (LADCR), Faculty of Science, Leiden University
• Date: 2023-11-09
• ISBN (print): 9789464833812