Synthesis and biological activity of small peptides as NOP and opioid receptors' ligands: view on current developments

Abstract

The heptadecapeptide nociceptin, also called orphanin FQ (N/OFQ), is the endogenous agonist of the N/OFQ peptide receptor (NOP receptor) and is involved in several central nervous system pathways, such as nociception, reward, tolerance, and feeding. The discovery of small molecule ligands for NOP is being actively pursued for several therapeutic applications. This review presents overview of the several recently reported NOP ligands (agonists and antagonists), with an emphasis of the structural features that may be important for modulating the intrinsic activity of these ligands. In addition, a brief account on the characterization of newly synthesized ligands of NOP receptor with aminophosphonate moiety and β-tryptophan analogues will be presented.

Keywords: Agonist; Analgesic effects; Antagonist; Hexapeptide analogues; NOP receptor; Nociceptin analogues; Nociceptin/orphanin FQ; Opioid peptides; SPPS.