Synthesis and biological activity of nociceptin/orphanin FQ(1–13)NH2 analogues modified in 9 and/or 13 position

The purpose of the present study was the synthesis and the biological screening of new analogues of N/OFQ(1–13)NH2, the minimal sequence maintaining the same activity as the natural peptide nociceptin. In order to investigate the role of Lys, we substituted Lys at positions 9 and/or 13 by Orn, Dab (diaminobutanoic acid) or Dap (diaminopropanoic acid). The new N/OFQ(1–13)NH2 analogues exerted strong and naloxone-resistant inhibition of electrically evoked contractions of rat vas deferens. Lys replacement with Orn maintained or even enhanced the inhibitory activity, while replacements with Dab and Dap decreased inhibitory activity.

Graphical abstractH-Phe-Gly-Gly-Phe-Thr-Gly-Ala-Arg-X9-Ser-Ala-Arg-X13-NH2X9,13 = Lys (1); X9 = Lys, X13 = Orn (2); X9 = Orn, X13 = Lys (3); X9,13 = Orn (4); X9,13 = Dab (5); X9,13 = Dap (6). The biological activities of the parent compound and its analogues were tested in vitro on electrically stimulated rat vas deferens.