Design, synthesis and biological evaluation of bivalent ligands against A(1)-D(1) receptor heteromers.

ABSTRACT:

Aim

To design and synthesize bivalent ligands for adenosine A1-dopamine D1 receptor heteromers (A1-D1R), and evaluate their pharmacological activities.

Methods

Bivalent ligands and their corresponding A1R monovalent ligands were designed and synthesized. The affinities of the bivalent ligands for A1R and D1R in rat brain membrane preparation were examined using radiolabeled binding assays. To demonstrate the formation of A1-D1R, fluorescence resonance energy transfer (FRET) was conducted in HEK293 cells transfected with D1-CFP and A1-YFP. Molecular modeling was used to analyze the possible mode of protein-protein and protein-ligand interactions.

Results

Two bivalent ligands for A1R and D1R (20a, 20b), as well as the corresponding A1R monovalent ligands (21a, 21b) were

SUBMITTER: Shen J 

PROVIDER: S-EPMC4002486 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature