Topological Exploration of Cyclic Endomorphin-1 Analogues, Structurally Defined Models for Investigating the Bioactive Conformation of MOR Agonists

Although there have been several reports on the conformational analysis of endomorphin-1 (YPWF-NH2) and related MOR (μ-opioid receptor) agonists, a definitive, convincing model of the biologically active structure is not yet available. We recently reported the synthesis and pharmacological characterization of the atypical endomorphin-analogue agonist c[YpwFG]. In this paper we discuss the conformational analysis of c[YpwFG] in comparison to its epimers, for investigating the topological features responsible for ligand recognition and receptor activation, and the role of the different pharmacophores.