Urotensin core mimics that modulate the biological activity of urotensin-II related peptide but not urotensin-II. - Archive ouverte HAL Access content directly
Journal Articles Bioorganic and Medicinal Chemistry Letters Year : 2017

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

(1, 2) , (3, 4) , (3, 4) , (2)
1
2
3
4

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.
Not file

Dates and versions

pasteur-01574618 , version 1 (15-08-2017)

Identifiers

Cite

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 and Medicinal Chemistry Letters, 2017, 27 (15), pp.3412-3416. ⟨10.1016/j.bmcl.2017.05.088⟩. ⟨pasteur-01574618⟩

Collections

RIIP INRS-IAF
161 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More