Are receptors acting as dimers?
Antonios Drakopoulos graduated from the University of Athens as a trained pharmacist and joined the International DoctorateProgram „Receptor Dynamics” within the medicinal chemistry group of Professor Decker at the University of Würzburg.
There is quite conflicting data whether G protein-coupled receptors (GPCRs) mediating the action of such well-known compounds as adrenaline and morphine, can associate forming dimers or even higher order oligomers. Antonios has chosen the therapeutically highly relevant opioid receptors, for which a lot of data has been collected so far, in order to investigate this behavior. He envisaged a “direct” way to check for dimerization by developing a ligand specifically binding to one receptor subtype, but which was labeled with fluorescent dyes. By using high-end microscopy techniques, he was then able to use these molecular probes to directly observe whether the native, i.e. the non-genetically modified receptor, associates to form dimers.
By using these probes, he could show that - at least the κ subtype of the receptor - does not form dimers on the membrane under the conditions applied. At the moment, he uses similar probes for the other opioid receptor subtypes, including the µ receptor, where all strong analgesics like morphine bind. These experiments are also aiming at investigating whether dimerization may take place there.
Antonios has synthesized his chemical compounds in the pharmaceutical and medicinal chemistry group and was able to apply them to investigate receptor dimerization at Birmingham University, UK, in the group of Professor Davide Calebiro (Institute of Metabolism and Systems Research and Centre of Membrane Proteins and Receptors). His research stay abroad was funded by the Elite Network of Bavaria.
Prior to publication of his results, Antonios has traveled to the most important medicinal chemistry symposium in Europe to attend the 6th “Young Medicinal Chemist Symposium” of the European Federation of Medicinal Chemistry in Athens, Greece. He was awarded one of the 2019 poster prizes for his scientific work.
Text: International Doctorate Program "Receptor Dynamics"