Heterobivalent Ligand for the Adenosine A_2A-Dopamine D₂ Receptor Heteromer.

ABSTRACT: A G protein-coupled receptor heteromer that fulfills the established criteria for its existence in vivo is the complex between adenosine A_2A (A_2AR) and dopamine D₂ (D₂R) receptors. Here, we have designed and synthesized heterobivalent ligands for the A_2AR-D₂R heteromer with various spacer lengths. The indispensable simultaneous binding of these ligands to the two different orthosteric sites of the heteromer has been evaluated by radioligand competition-binding assays in the absence and presence of specific peptides that disrupt the formation of the heteromer, label-free dynamic mass redistribution assays in living cells, and molecular dynamic simulations. This combination of techniques has permitted us to identify com

SUBMITTER: Pulido D 

PROVIDER: S-EPMC11915710 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature