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.

Urotensin II(4-11) Azasulfuryl Peptides: Synthesis and Biological Activity / Merlino, Francesco; Yousif, ALI MUNAIM; Billard, Étienne; Dufour Gallant, Julien; Turcotte, Stéphane; Grieco, Paolo; Chatenet, David; Lubell, William D.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 59:10(2016), pp. 4740-4752. [10.1021/acs.jmedchem.6b00108]

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

MERLINO, FRANCESCO
Co-primo
;
YOUSIF, ALI MUNAIM
Co-primo
;
GRIECO, PAOLO;CHATENET, DAVID;
2016

Abstract

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.
2016
Urotensin II(4-11) Azasulfuryl Peptides: Synthesis and Biological Activity / Merlino, Francesco; Yousif, ALI MUNAIM; Billard, Étienne; Dufour Gallant, Julien; Turcotte, Stéphane; Grieco, Paolo; Chatenet, David; Lubell, William D.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 59:10(2016), pp. 4740-4752. [10.1021/acs.jmedchem.6b00108]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/636768
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