Title: In Vitro Studies of the Activity of Newly Sinthesized Nociceptin / Orphanin FQ Receptor Ligand Analogues
Volume: 17
Issue: 5
Author(s): L. Kasakov, M. Nashar, E. Naydenova, L Vezenkov and M. Vlaskovska
Affiliation:
Keywords:
NOP receptor ligands, structure-activity relationship, rat vas deferens, neurogenic contraction
Abstract: Based on template hexapeptides Ac-Arg-Tyr-Tyr-Arg-Trp-Lys-NH2 and Ac-Arg-Tyr-Tyr-Arg-Ile-Lys-NH2 analogues and corresponding deacylated homologues were synthesized substituting ornithine, diaminobutanoic (Dab) and diaminopropanoic (Dap) acids for lysine at position 6. The aim was to investigate the effect of the newly synthesized compounds on the neurogenic contractions of isolated rat vas deferens. Ac-Arg-Tyr-Tyr-Arg-Trp-Lys-NH2 and its analogues manifested a strong inhibitory effect on the neurogenic contractions without effect on the muscle tone, which is characteristic effect of NOP receptor agonists. In contrast, Ac-Arg-Tyr-Tyr-Arg-Ile-Lys-NH2 and its analogs manifested a strong inhibitory effect on the muscle tone and negligible effect on the neurogenic contractions which is characteristic effect of NOP receptor antagonists. The most active were the peptides in which Dab or Dap is the substitute. The study reveals that substitution of Lys with shorter amino acids could increase agonist or antagonist activity of the peptide.
