Media type: E-Article Title: Solution structure of nociceptin peptides Contributor: Amodeo, Pietro; Guerrini, Remo; Picone, Delia; Salvadori, Severo; Spadaccini, Roberta; Tancredi, Teodorico; Temussi, Piero A. imprint: Wiley, 2002 Published in: Journal of Peptide Science Language: English DOI: 10.1002/psc.412 ISSN: 1075-2617; 1099-1387 Keywords: Organic Chemistry ; Drug Discovery ; Pharmacology ; Molecular Biology ; Molecular Medicine ; General Medicine ; Biochemistry ; Structural Biology Origination: Footnote: Description: <jats:title>Abstract</jats:title><jats:p>Peptides embedded in the sequence of pre‐pro‐nociceptin, i.e. nociceptin, nocistatin and orphanin FQ2, have shed light on the complexity of the mechanisms involving the peptide hormones related to pain and have opened up new perspectives for the clinical treatment of pain. The design of new ligands with high selectivity and bioavailability, in particular for ORL1, is important both for the elucidation and control of the physiological role of the receptor and for their therapeutic importance. The failure to obtain agonists and antagonists when using, for nociceptin, the same substitutions that are successful for opioids, and the conformational flexibility of them all, justify systematic efforts to study the solution conformation under conditions as close as possible to their natural environment. Structural studies of linear peptides in solution are hampered by their high flexibility. A direct structural study of the complex between a peptide and its receptor would overcome this difficulty, but such a study is not easy since opioid receptors are membrane proteins. Thus, conformational studies of lead peptides in solution are still important for drug design. This review deals with conformational studies of natural pre‐nociceptin peptides in several solvents that mimic in part the different environments in which the peptides exert their action. None of the structural investigations yielded a completely reliable bioactive conformation, but the global conformation of the peptides in biomimetic environments can shed light on their interaction with receptors. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd.</jats:p>