Synthesis and binding activity of endomorphin-1 analogues containing β-amino acids

Endomorphin-1 (Tyr-Pro-Trp-PheNH(2)) has been proposed as the most potent endogenous ligand of the mu -opioid receptors. In this paper, we describe the synthesis of some endomorphin-1 based tetrapeptides in which a residue of the sequence Tyr-Pro-Trp-PheNH(2) is replaced by the corresponding beta -isomer. These novel peptides showed different affinities for the opioid receptors labeled with [H-3]-DAMGO in rat brain membranes, depending on the beta -amino acid. In particular, the tetrapeptide containing beta -Pro (Tyr-beta-(R)-Pro-Trp-PheNH(2)) displayed a higher affinity than endogenous endomorphin-1, as revealed by their K-i values (0.33 and 11.1 nM, respectively). (C) 2000 Elsevier Science Ltd. All rights reserved.