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Urotensin II(4–11) Azasulfuryl Peptides: Synthesis and Biological Activity

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journal contribution
posted on 03.05.2016, 00:00 by Francesco Merlino, Ali M. Yousif, Étienne Billard, Julien Dufour-Gallant, Stéphane Turcotte, Paolo Grieco, David Chatenet, William D. Lubell
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 611 by routes featuring alkylation of azasulfuryl-glycine tripeptide precursors to install various side chains. The pharmacological profiles of derivatives 611 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 79 reduced up to 50% of the effects of UII and urotensin II-related peptide (URP) without affecting their potency.