Structure-Activity Relationships of [des-Arg⁷]Dynorphin A Analogues at the κ Opioid Receptor.

ABSTRACT: Dynorphin A (Dyn A) is an endogenous ligand for the opioid receptors with preference for the κ opioid receptor (KOR), and its structure-activity relationship (SAR) has been extensively studied at the KOR to develop selective potent agonists and antagonists. Numerous SAR studies have revealed that the Arg⁷ residue is essential for KOR activity. In contrast, our systematic SAR studies on [des-Arg⁷]Dyn A analogues found that Arg⁷ is not a key residue and even deletion of the residue does not affect biological activities at the KOR. In addition, it was also found that [des-Arg⁷]Dyn A(1-9)-NH₂ is a minimum pharmacophore and its modification at the N-terminus leads to selective KOR antagonists. A lead ligand, 14, with high affinity and antag

SUBMITTER: Ramos-Colon CN 

PROVIDER: S-EPMC5693303 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature