Novel [D-Arg²]dermorphin(1—4) Analogs with μ-Opioid Receptor Antagonist Activity

Abstract

Ten Tyr-D-Arg-Phe-βAla-NH₂ (YRFB) analogs in which specific amino acid side chains are shifted to the N^α-position were synthesized, and the binding to these analogs to the μ receptor and their in vitro biological properties were evaluated. Some analogs in which a N,N-bis(p-hydroxybenzyl)-Gly residue was substituted for Tyr¹ exhibited μ receptor antagonist activities (pA₂) between 5.3 and 6.1. Of these analogs, [N,N-bis(p-hydroxybenzyl)-Gly¹]YRFB was found to be the most potent specific antagonist for the μ-opioid receptor.