Development and Pharmacological Characterization of Conformationally Constrained Urotensin II-Related Peptide Agonists
| Autor: | Debby Feytens, Nicolas Doucet, Myriam Létourneau, Alain Fournier, David Chatenet, Dirk Tourwé, Benjamin Folch |
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| Přispěvatelé: | Institut Armand Frappier (INRS-IAF), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), International Associated laboratory Samuel de Champlain, Institut National de la Recherche Scientifique [Québec] (INRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Organic Chemistry, Vrije Universiteit Brussel (VUB), PROTEO, The Quebec Network for Research on Protein Function, Engineering, and Applications, Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS)-Université de Sherbrooke (UdeS)-Université Laval [Québec] (ULaval)-McGill University = Université McGill [Montréal, Canada]-University of Ottawa [Ottawa]-Université du Québec à Trois-Rivières (UQTR)-Université de Montréal (UdeM)-TransBiotech, Lévis-Concordia University [Montreal]-Université du Québec à Montréal = University of Québec in Montréal (UQAM), Groupe de Recherche Axé sur la Structure des Protéines (GRASP), McGill University = Université McGill [Montréal, Canada], This work was supported by CIHR grants (awarded to A.F.), NSERC Discovery Grant RGPIN 402623-2011 (awarded to N.D.) |
| Rok vydání: | 2013 |
| Předmět: |
Male
Stereochemistry [SDV]Life Sciences [q-bio] Peptide Hormones Urotensins Aorta Thoracic Peptide Molecular Dynamics Simulation 01 natural sciences 03 medical and health sciences chemistry.chemical_compound Residue (chemistry) Drug Discovery Animals Receptor 030304 developmental biology Indole test chemistry.chemical_classification 0303 health sciences 010405 organic chemistry Intracellular Signaling Peptides and Proteins Receptor interaction Urotensin II-related peptide Rats 0104 chemical sciences Amino acid chemistry Vasoconstriction [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology Molecular Medicine Urotensin-II |
| Zdroj: | Journal of Medicinal Chemistry Journal of Medicinal Chemistry, American Chemical Society, 2013, 56 (23), pp.9612-22. ⟨10.1021/jm401153j⟩ |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm401153j |
| Popis: | International audience; Urotensin II (UII) and its paralog peptide, urotensin II-related peptide (URP), exert not only common but also divergent actions through the activation of UT, a specific membrane-bound receptor that belongs to the 1A G protein-coupled receptor subclass. In this study, we have designed and synthesized new URP analogues in which the intracyclic Trp residue was replaced with natural, unnatural, and constrained amino acids to determine important physicochemical features for receptor binding and activation. The biological data, highlighting the potent agonistic behavior of [Tiq(4)]URP and [Tpi(4)]URP, also suggest that the Trp residue, and more specifically the indole ring, is not critical for receptor interaction and could in fact be involved in the intramolecular stabilization of the bioactive conformation of URP. Finally, these analogues, which are intracyclic constrained URP-based agonists, could represent useful pharmacological tools for the study of the urotensinergic system. |
| Databáze: | OpenAIRE |
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