Merlino, Francesco; Yousif, Ali Munaim; Billard, Étienne; Dufour-Gallant, Julien; Turcotte, Stéphane; Grieco, Paolo; Chatenet, David et Lubell, William D (2016). Urotensin II(4-11) Azasulfuryl Peptides: Synthesis and Biological Activity Journal of Medicinal Chemistry , vol. 59 , nº 10. pp. 4740-4752. DOI: 10.1021/acs.jmedchem.6b00108.
Ce document n'est pas hébergé sur EspaceINRS.Résumé
Cyclic azasulfuryl (As) peptide analogs of the urotensin II (UII, 1, H-Glu-Thr-Pro-Asp-c[Cys-Phe-Trp-Lys-Tyr-Cys]-Val-OH) fragment 4-11 were synthesized to explore the influences of backbone structure on biological activity. N-Aminosulfamides were inserted as surrogates of the Trp7 and Lys8 residues in the biologically relevant Trp-Lys-Tyr triad. A combination of solution- and solid-phase methods were used to prepare novel UII(4-11) analogs 6-11 by routes featuring alkylation of azasulfuryl-glycine tripeptide precursors to install various side chains. The pharmacological profiles of derivatives 6-11 were tested in vitro using a competitive binding assay and ex vivo using a rat aortic ring bioassay. Although the analogs exhibited weak affinity for the urotensin II receptor (UT) without agonistic activity, azasulfuryl-UII(4-11) derivatives 7-9 reduced up to 50% of the effects of UII and urotensin II-related peptide (URP) without affecting their potency. © 2016 American Chemical Society.
| Type de document: | Article |
|---|---|
| Mots-clés libres: | II RECEPTOR ANTAGONIST; PHARMACOPHORE MODEL; AMINO-ACID; EX-VIVO; ATHEROSCLEROSIS; INHIBITION; ACTIVATION; MODULATORS; ANALOGS; DESIGN |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 16 mai 2017 20:32 |
| Dernière modification: | 07 déc. 2020 15:07 |
| URI: | https://espace.inrs.ca/id/eprint/4615 |
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