Year: 2020
Type: dissertation
Abstract: G-protein coupled receptors (GPCRs) constitute a large family of 7-transmembrane domain proteins that transduce extracellular signals to a cell’s interior. Approximately 35% of all FDA-approved drugs target a disproportionally small part of this family. As our understanding of these receptors continues to evolve, developments in drug discovery focus on facilitating the identification of novel orthosteric and allosteric druggable sites. In this work, an attempt was made to employ fragment-based drug discovery (FBDD) for the adenosine 2A receptor (A2AR), expressed in P. pastoris, via electron paramagnetic resonance (EPR). This technique uses unpaired electrons to provide information on conformation, local topology, and dynamics. In this study, spin labeled A2AR ligands were synthesized, in order to observe ligand binding to A2AR and develop a competition assay to observe drug binding. To enhance the magnitude of EPR spectral changes, an amino-terminal copper and nickel binding (ATCUN) motif was installed at the N-terminus of A2AR.
Source: TSpace (University of Toronto)
Author: Jacob Van Reet
Language: English
Subfield: Spectroscopy
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W3163698405