Chatenet, David 
ORCID: https://orcid.org/0000-0002-7270-4328; Dubessy, Christophe; Boularan, Cédric; Scalbert, Elizabeth; Pfeiffer, Bruno; Renard, Pierre; Lihrmann, Isabelle; Pacaud, Pierre; Tonon, Marie-Christine; Vaudry, Hubert et Leprince, Jérôme
(2006).
Structure-activity relationships of a novel series of urotensin II analogues: identification of a urotensin II antagonist
Journal of Medicinal Chemistry
, vol. 49
, nº 24.
pp. 7234-7238.
DOI: 10.1021/jm0602110.
Résumé
Urotensin II (U-II) is a potent vasoconstrictor peptide which has been identified as the endogenous ligand for the orphan G protein-coupled receptor GPR14 now renamed UT receptor. As the C-terminal cyclic hexapeptide of U-II (U-II(4-11), H-Asp-Cys-Phe-Trp-Lys-Tyr-Cys-Val-OH) possesses full biological activity, we have synthesized a series of U-II(4-11) analogues and measured their binding affinity on hGPR14-transfected CHO cells and their contractile activity on de-endothelialized rat aortic rings. The data indicate that a free amino group and a functionalized side-chain at the N-terminal extremity of the peptide are not required for biological activity. In addition, the minimal chemical requirement at position 9 of U-II(4-11) is the presence of an aromatic moiety. Most importantly, replacement of the Phe6 residue by cyclohexyl-Ala (Cha) led to an analogue, [Cha6]U-II(4-11), that was devoid of agonistic activity but was able to dose-dependently suppress the vasoconstrictor effect of U-II on rat aortic rings. These new pharmacological data, by providing further information regarding the structure-activity relationships of U-II analogues, should prove useful for the rational design of potent and nonpeptidic UT receptor agonists and antagonists.
| Type de document: | Article |
|---|---|
| Mots-clés libres: | - |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 22 oct. 2024 19:46 |
| Dernière modification: | 22 oct. 2024 19:46 |
| URI: | https://espace.inrs.ca/id/eprint/14487 |
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