Discovery of Dermorphin-Based Affinity Labels with Subnanomolar Affinity for Mu Opioid Receptors

Abstract

A series of potent electrophilic affinity labels (IC(50) = 0.1-5 nM) containing either a bromoacetamide or isothiocyanate based on the mu opioid receptor (MOR) selective peptide dermorphin were prepared. All four analogues exhibited wash resistant inhibition of [(3)H]DAMGO binding at subnanomolar to nanomolar concentrations, suggesting that these analogues bind covalently to MOR. To our knowledge, these peptides are the highest affinity peptide-based affinity labels for MOR reported to date.