Structure-activity study of the nociceptin(1-13)-NH2 N-terminal tetrapeptide and discovery of a nociceptin receptor antagonist.

摘要: In the present study, minimal fragment sequence required to fully activate nociceptin (NC) receptor, namely NC(1−13)-NH2, was used as template for design of a series new compounds. Changes were made in N-terminal tetrapeptide Phe-Gly-Gly-Phe, which has been shown be essential receptor occupation and activation. The compounds tested their ability inhibit electrically evoked contraction mouse vas deferens, pharmacological preparation sensitive NC. Results obtained indicate that (a) replacement Gly2 or Gly3 with an aromatic residue (Phe) l d chirality eliminates peptide occupy NC receptor; (b) distance between Phe1 Phe4 appears critical, since any alteration it leads marked decrease total elimination biological activity; (c) insertion pseudopeptide bond maintains affinity but an...