title: Synthesis and biological activity of novel small peptides with aminophosphonates moiety as NOP receptor ligands.
abstract: The aim of the present study was the synthesis and the biological screening of new analogs of Ac-RYYRWK-NH2, modified at the N-terminal with 1-[(methoxyphosphono)methylamino]cycloalkanecarboxylic acids. The four newly synthesized ligands for the nociceptin/orphanin FQ (N/OFQ) receptor (NOP) have been prepared by solid-phase peptide synthesis--Fmoc-strategy. These compounds were tested for agonistic activity in vitro on electrically stimulated smooth-muscle preparations isolated from vas deferens of Wistar rats. Our data showed that substitution of Arg at position 1 with aminophosphonates moiety decreased significantly the affinity of ligands to the NOP receptor. Furthermore, the enlargement of the cycle (with 5-8 carbon atoms) additionally diminished both the activity and the selectivity for NOP-receptor.
authors.affiliation: Department of Organic Chemistry, University of Chemical Technology and Metallurgy, 1756, Sofia, Bulgaria. e_naydenova@abv.bg
authors.forename: Emilia D
authors.initials: ED
authors.lastname: Naydenova
authors.forename: Petar T
authors.initials: PT
authors.lastname: Todorov
authors.forename: Polina I
authors.initials: PI
authors.lastname: Mateeva
authors.forename: Rositza N
authors.initials: RN
authors.lastname: Zamfirova
authors.forename: Nikola D
authors.initials: ND
authors.lastname: Pavlov
authors.forename: Simeon B
authors.initials: SB
authors.lastname: Todorov
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D008024:Ligands; D008297:Male; D015394:Molecular Structure; D008970:Molecular Weight; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D063065:Organophosphonates / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014649:Vas Deferens / Q000187:drug effects* / Q000502:physiology; D000094942:Nociceptin Receptor
chemical_list: D008024:Ligands; D063065:Organophosphonates; D010455:Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; C000722285:Oprl1 protein, rat