title: Synthesis and biological activity of new series of N-modified analogues of the N/OFQ(1-13)NH2 with aminophosphonate moiety.
abstract: New series of N-modified analogues of the N/OFQ(1-13)NH(2) with aminophosphonate moiety have been synthesized and investigated for biological activity. These peptides were prepared by solid-phase peptide synthesis-Fmoc-strategy. The N/OFQ(1-13)NH(2) analogues were tested for agonistic activity in vitro on electrically stimulated rat vas deferens smooth-muscle preparations isolated from Wistar albino rats. Our study has shown that the selectivity of the peptides containing 1-[(methoxyphosphono)methylamino]cycloalkanecarboxylic acids to the N-side of Phe is not changed-they remain selective agonists of NOP receptors. The derivative with the largest ring (NOC-6) demonstrated efficacy similar to that of N/OFQ(1-13)NH(2), but in a 10-fold higher concentration. The agonistic activity of newly synthesized N-modified analogues of N/OFQ(1-13)NH(2) with aminophosphonate moiety was investigated for the first time.
authors.affiliation: Department of Organic Chemistry, University of Chemical Technology and Metallurgy, Sofia, Bulgaria.
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: Emilia D
authors.initials: ED
authors.lastname: Naydenova
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D018847:Opioid Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D063065:Organophosphonates / Q000138:chemical synthesis / Q000494:pharmacology*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000819:agonists*; D013329:Structure-Activity Relationship; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D018847:Opioid Peptides; D063065:Organophosphonates; D010446:Peptide Fragments; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722285:Oprl1 protein, rat