Synthesis and receptor binding properties of chimeric peptides containing a μ-opioid receptor ligand and nociceptin/orphanin FQ receptor ligand Ac-RYYRIK-amide

Four chimera peptides composed of ORL1 receptor ligand Ac-RYYRIK-NH2 and a μ-opioid receptor agonist dermorphin YAFGYPS-NH2 or YRFB-NH2, with a spacer linking the two pharmacophores, were synthesized and tested for their receptor binding properties. Chimera peptides with long spacers (a Lys and five or eight Gly residues) showed synergistically improved affinity for both the μ-opioid receptor and ORL1 receptor, while the chimera peptides with short spacers (Lys residue only) showed decreased or similar affinity compared to the monomeric receptor ligands. Chimera peptides containing long spacers may prove to be useful tools for studying ORL1 receptor/μ-opioid receptor heterodimers.