Synthesis and Pharmacological Characterization of Nociceptin/Orphanin FQ Dimeric Ligands.

ABSTRACT: The neuropeptide nociceptin/orphanin FQ (N/OFQ) plays a key role in regulating several physiological functions and pathological states, which makes its receptor (NOP) a promising target for therapeutic interventions. In this study, we synthesized homodimeric N/OFQ-NH₂ derivatives linked by disulfide bonds between cysteines appropriately introduced in the addressing region of the native peptide in place of the original amino acids. The in vitro activity of the compounds was evaluated using both an NOP-G protein interaction BRET assay and a calcium mobilization assay. The most potent compound, 1h (pEC₅₀ > 9), was obtained by coupling two monomeric precursors via a Leu¹⁴-to-Cys substitution. In vivo, 1h demonstrated 3-fold greater p

SUBMITTER: Albanese V 

PROVIDER: S-EPMC12621184 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature