Synthesis and biological activity of novel small peptides with aminophosphonates moiety as NOP receptor ligands.
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.
Naydenova
Emilia D
ED
Department of Organic Chemistry, University of Chemical Technology and Metallurgy, 1756, Sofia, Bulgaria. e_naydenova@abv.bg
Todorov
Petar T
PT
Mateeva
Polina I
PI
Zamfirova
Rositza N
RN
Pavlov
Nikola D
ND
Todorov
Simeon B
SB
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
D008024:Ligands; D063065:Organophosphonates; D010455:Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; C000722285:Oprl1 protein, rat