Allosteric modulation of dopamine D_2L receptor in complex with G_i1 and G_i2 proteins: the effect of subtle structural and stereochemical ligand modifications.

ABSTRACT:

Background

Allosteric modulation of G protein-coupled receptors (GPCRs) is nowadays one of the hot topics in drug discovery. In particular, allosteric modulators of D₂ receptor have been proposed as potential modern therapeutics to treat schizophrenia and Parkinson's disease.

Methods

To address some subtle structural and stereochemical aspects of allosteric modulation of D₂ receptor, we performed extensive in silico studies of both enantiomers of two compounds (compound 1 and compound 2), and one of them (compound 2) was synthesized as a racemate in-house and studied in vitro.

Results

Our molecular dynamics simulations confirmed literature reports that the R enantiomer of compound 1 is a positive allosteric modulator of the D_2L recepto

SUBMITTER: Zuk J 

PROVIDER: S-EPMC8964653 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature