Mechanistic Understanding of Peptide Analogues, DALDA, [Dmt¹]DALDA, and KGOP01, Binding to the mu Opioid Receptor.

ABSTRACT: The mu opioid receptor (MOR) is the primary target for analgesia of endogenous opioid peptides, alkaloids, synthetic small molecules with diverse scaffolds, and peptidomimetics. Peptide-based opioids are viewed as potential analgesics with reduced side effects and have received constant scientific interest over the years. This study focuses on three potent peptide and peptidomimetic MOR agonists, DALDA, [Dmt¹]DALDA, and KGOP01, and the prototypical peptide MOR agonist DAMGO. We present the first molecular modeling study and structure-activity relationships aided by in vitro assays and molecular docking of the opioid peptide analogues, in order to gain insight into their mode of binding to the MOR. In vitro binding and functional assays revealed the same rank order with KGOP01 >

SUBMITTER: Dumitrascuta M 

PROVIDER: S-EPMC7248707 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature