Unknown

Dataset Information

0

Equipotent enantiomers of cyclic opioid peptides at ? opioid receptor.


ABSTRACT: Head-to-tail cyclized analogues of the ? opioid receptor (MOR) agonist tetrapeptides DALDA (H-Tyr-D-Arg-Phe-Lys-NH2 and [Dmt1]DALDA (H-Dmt-D-Arg-Phe-Lys-NH2; Dmt = 2',6'-dimethyltyrosine) and their enantiomers (mirror-image isomers) were synthesized and pharmacologically characterized in vitro. Three pairs of enantiomeric cyclic peptides with both mirror-image isomers having equipotent MOR binding affinities but different binding affinities at the ? and ? opioid receptors were identified. The cyclic peptide enantiomers c[-D-Arg-Phe-Lys-Tyr-] (1) and c[-Arg-D-Phe-D-Lys-D-Tyr-] (2) showed nearly identical MOR binding affinity (1 - 2 nM) and equipotent MOR antagonist activity. The results of a MOR docking study indicated a very similar binding mode of the two enantiomers with nearly complete spatial overlap of the peptide ring structures and side chain interactions with the same MOR residues. Compounds 1 and 2 represent the first pair of enantiomeric G-protein-coupled receptor (GPCR) ligands having multiple chiral centers, with both optical antipodes showing equal, low nanomolar receptor binding affinity.

SUBMITTER: Weltrowska G 

PROVIDER: S-EPMC6383560 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC5693220 | biostudies-literature
2023-01-01 | GSE218564 | GEO
| S-EPMC10352325 | biostudies-literature
| S-EPMC6722706 | biostudies-literature
| S-EPMC5253357 | biostudies-literature
| S-EPMC7491576 | biostudies-literature
| S-EPMC7444290 | biostudies-literature
| S-EPMC7881245 | biostudies-literature
| S-EPMC5222732 | biostudies-literature
| S-EPMC4202600 | biostudies-literature