Synthesis and changes in affinity for NOP and opioid receptors of novel hexapeptides containing b2-tryptophan analogues.

Rositsa Zamfirova (1) , Nikola Pavlov (2) , Petar Todorov (2) , Polina Mateeva (1) , Jean Martinez (3) , Monique Calmes (3) , Emilia Naydenova (2)

1 Institute of Neurobiology
2 Department of Organic Chemistry
3 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]

We report the synthesis and the biological activity of new analogues of Ac-RFMWMK-NH2 and Ac- RYYRWK-NH2, modified in position 4 and 5, respectively, with incorporation of newly synthesized b2- tryptophan analogues. Trp was substituted by the (S)-2-(1-methyl-1H-indol-3-yl)propionic residue or by (S)-2-(5-methoxy-1H-indol-3-yl)propionic residue. The biological activity (pEC50 and Emax) of these compounds was tested on electrically stimulated preparations of rat vas deferens. The 5-methoxy b-tryptophan group reverses the affinity of the compounds.

Mots clés: Nociceptin analogue; Nociceptin/orphanin FQ-NOP receptor; b-Tryptophan analogues; Rat vas deferens

Domaines: Chimie organique

Rositsa Zamfirova, Nikola Pavlov, Petar Todorov, Polina Mateeva, Jean Martinez, et al.. Synthesis and changes in affinity for NOP and opioid receptors of novel hexapeptides containing b2-tryptophan analogues.. Bioorganic and Medicinal Chemistry Letters, 2013, 23, pp.4052-4055. ⟨10.1016/j.bmcl.2013.05.064⟩. ⟨hal-00969102⟩