title: Urotensin II((4-11)) Azasulfuryl Peptides: Synthesis and Biological Activity.
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.
authors.affiliation: Département de Chimie, Université de Montréal , C.P. 6128, Station Centre-ville, Montréal, Québec H3C 3J7, Canada.|Department of Pharmacy, University of Naples "Federico II" , via D. Montesano 49, 80131 Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Merlino
authors.affiliation: Département de Chimie, Université de Montréal , C.P. 6128, Station Centre-ville, Montréal, Québec H3C 3J7, Canada.|Department of Pharmacy, University of Naples "Federico II" , via D. Montesano 49, 80131 Naples, Italy.
authors.forename: Ali M
authors.initials: AM
authors.lastname: Yousif
authors.affiliation: INRS - Institut Armand-Frappier, Groupe de Recherche en Ingénierie des Peptides et en Pharmacothérapie (GRIPP), Université du Quebéc , Ville de Laval, Quebec H7V 1B7, Canada.
authors.forename: Étienne
authors.initials: É
authors.lastname: Billard
authors.affiliation: Département de Chimie, Université de Montréal , C.P. 6128, Station Centre-ville, Montréal, Québec H3C 3J7, Canada.
authors.forename: Julien
authors.initials: J
authors.lastname: Dufour-Gallant
authors.affiliation: Département de Chimie, Université de Montréal , C.P. 6128, Station Centre-ville, Montréal, Québec H3C 3J7, Canada.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Turcotte
authors.affiliation: Department of Pharmacy, University of Naples "Federico II" , via D. Montesano 49, 80131 Naples, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Grieco
authors.affiliation: INRS - Institut Armand-Frappier, Groupe de Recherche en Ingénierie des Peptides et en Pharmacothérapie (GRIPP), Université du Quebéc , Ville de Laval, Quebec H7V 1B7, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Chatenet
authors.affiliation: Département de Chimie, Université de Montréal , C.P. 6128, Station Centre-ville, Montréal, Québec H3C 3J7, Canada.
authors.forename: William D
authors.initials: WD
authors.lastname: Lubell
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D016466:CHO Cells; D002478:Cells, Cultured; D003412:Cricetulus; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014579:Urotensins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D014579:Urotensins; C029677:urotensin II