Urotensin core mimics that modulate the biological activity of urotensin-II related peptide but not urotensin-II.

Martin Strack 1, 2 Étienne Billard 3, 4 David Chatenet 3, 4 William D Lubell 2
1 RUB - Ruhr University Bochum
2 Université de Montréal [Montréal]
3 INRS-IAF - Institut Armand Frappier
4 GRIPP - Groupe de Recherche en Ingénierie des Peptides et en Pharmacothérapie
Abstract : A novel approach for the synthesis of head-to-tail cyclic peptides has been developed and used to prepare two mimics of the urotensin II-related peptide (URP) cyclic core. Mimics 1 and 2 (c[Trp-Lys-Tyr-Gly-ψ(triazole)-Gly] and c[Phe-Trp-Lys-Tyr-Gly-ψ(triazole)-Gly]) were respectively prepared using a combination of solid- and solution-phase synthesis. The silyl-based alkyne-modifying (SAM) linker enabled installation of C-terminal alkyne and N-terminal azide moieties onto linear peptide precursors, which underwent head-to-tail copper-catalyzed azide-alkyne cycloaddition (CuAAC) in solution. In an aortic ring contraction assay, neither 1 nor 2 exhibited agonist activity; however, both inhibited selectively URP- but not UII-mediated vasoconstriction. The core phenylalanine residue was shown to be important for enhancing modulatory activity of the urotensinergic system.
Keywords : Allosteric modulator Head-to-tail cyclization Peptide mimicry SAM-linker Urotensin-II Urotensin-II related peptide
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Article dans une revue
Bioorganic & Medicinal Chemistry Letters, Elsevier, 2017, 27 (15), pp.3412-3416. 〈10.1016/j.bmcl.2017.05.088〉
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https://hal-riip.archives-ouvertes.fr/pasteur-01574618
Contributeur : Michel Courcelles <>
Soumis le : mardi 15 août 2017 - 22:26:35
Dernière modification le : lundi 5 février 2018 - 15:22:10

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Martin Strack, Étienne Billard, David Chatenet, William D Lubell. Urotensin core mimics that modulate the biological activity of urotensin-II related peptide but not urotensin-II.. Bioorganic & Medicinal Chemistry Letters, Elsevier, 2017, 27 (15), pp.3412-3416. 〈10.1016/j.bmcl.2017.05.088〉. 〈pasteur-01574618〉

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