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

Francesco Merlino (1, 2) , Ali M Yousif (1, 2) , Étienne Billard (3) , Julien Dufour-Gallant (1) , Stéphane Turcotte (1) , Paolo Grieco (2) , David Chatenet (3) , William D Lubell (1)

1 Departments of Chemistry
2 University of Naples Federico II = Università degli studi di Napoli Federico II
3 INRS-IAF - Institut Armand Frappier

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 Trp(7) and Lys(8) 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.

Domains: Life Sciences [q-bio]

Francesco Merlino, Ali M Yousif, Étienne Billard, Julien Dufour-Gallant, Stéphane Turcotte, et al.. Urotensin II((4-11)) Azasulfuryl Peptides: Synthesis and Biological Activity.. Journal of Medicinal Chemistry, 2016, 59 (10), pp.4740-52. ⟨10.1021/acs.jmedchem.6b00108⟩. ⟨pasteur-01351481⟩