title: Synthesis and analgesic effects of novel β2-tryptophan hexapeptide analogs.
abstract: Aiming to develop more potent analgesic substances a new series of hexapeptides containing β(2)-tryptophan analogues was synthesized. The Trp in position 4 and 5, respectively in Ac-Arg-Phe-Met-Trp-Met-Lys-NH2 (opioid receptor antagonist) and Ac-Arg-Tyr-Tyr-Arg-Trp-Lys-NH2 (highly potent and selective NOP-receptor agonist) was substituted by the (S)-2-(1-methyl-1H-indol-3-yl)propionic residue or the (S)-2-(5-methoxy-1H-indol-3-yl)propionic residue. The analgesic effect of the four newly synthesized compounds has been evaluated in male Wistar rats by PP- and HP tests and compared to the native templates. Further estimation of the mechanisms of action of each compound was achieved using specific antagonists-naloxone for opioid and JTC801 for the NOP receptor. Replacement of Trp with β(2)-tryptophan analogues in 4th position (Ac-Arg-Phe-Met-Trp-Met-Lys-NH2) led to increased and longer lasting analgesic effect. The results obtained permit us to assume that both opioid and NOP receptors take part in the newly synthesized compounds analgesic effects.
authors.affiliation: Department of Pathophysiology, Faculty of Medicine, Medical University, Sofia, 1431, Bulgaria.
authors.forename: Adriana
authors.initials: A
authors.lastname: Bocheva
authors.forename: Hristina
authors.initials: H
authors.lastname: Nocheva
authors.forename: Nikola
authors.initials: N
authors.lastname: Pavlov
authors.forename: Petar
authors.initials: P
authors.lastname: Todorov
authors.forename: Monique
authors.initials: M
authors.lastname: Calmès
authors.forename: Jean
authors.initials: J
authors.lastname: Martinez
authors.forename: Emilia
authors.initials: E
authors.lastname: Naydenova
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D008297:Male; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D000700:Analgesics; D009842:Oligopeptides; D014364:Tryptophan