Related Experiment Video
Updated: Jan 12, 2026

Preparation and Delivery of Protein Microcrystals in Lipidic Cubic Phase for Serial Femtosecond Crystallography
Published on: September 20, 2016
Synthesis and Pharmacological Characterization of Nociceptin/Orphanin FQ Dimeric Ligands
Valentina Albanese1, Pietro Pola2, Michela Argentieri2
1Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via Luigi Borsari 46, 44121 Ferrara, Italy.
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 potency than N/OFQ in eliciting loss of the righting reflex in mice and produced a long-lasting effect monitored for up to 7 h, supporting multimerization as a viable approach to developing long-acting peptide-based NOP ligands.
Related Concept Videos
Opioid Receptors: Overview
Drug-Receptor Interaction: Agonist
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous...
Nociception
Analgesia and Pain Management
Opioid Analgesics: Synthetic and Semisynthetic Opioids
The Two-State Receptor Model
The binding affinity of a drug determines its interaction with...

