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Visualizing a receptor

Anto­nios Drakopoulos de­signed and syn­the­sized novel com­pounds that are able to specif­ically bind to one recep­tor sub­type of the opioid recep­tors, which is thus con­nected chem­ically to a fluo­rescent dye. These com­pounds ena­ble visual­izing single native recep­tors on the mem­branes of cells by high-end sin­gle-mol­ecule mi­cros­copy.

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.

Poster Award

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"