title: Structure-activity relationship study on human urotensin II.
abstract: The vasoactive cyclic undecapeptide urotensin-II (U-II) has been identified as an endogenous ligand for the G-protein coupled receptor now referred to as the UT receptor. The U-II/UT receptor system might be relevant for cardiovascular functions. A structure-activity study of human U-II investigating 31 peptides in the rat aorta bioassay is reported. Ala- and D-scan investigations indicated that the sequence Phe6-Trp7-Lys8-Tyr9 is essential for biological activity and that Lys8 and Tyr9 are particularly important. These two residues were substituted with a series of coded and non-coded amino acids. These studies demonstrated that the positive charge of the primary aliphatic amine at position 8 and its relative spatial orientation is crucial for both receptor occupation and activation, while the only chemical requirement at position 9 is the presence of an aromatic moiety. Moreover, this study led to the identification of UT receptor partial agonists (compounds 23 and 24) which can be used as chemical templates for further investigations aimed at the identification of selective antagonists.
authors.affiliation: Department of Pharmaceutical Sciences and Biotechnology Centre, University of Ferrara, 44100 Ferrara, Italy.
authors.forename: Remo
authors.initials: R
authors.lastname: Guerrini
authors.forename: Valeria
authors.initials: V
authors.lastname: Camarda
authors.forename: Erika
authors.initials: E
authors.lastname: Marzola
authors.forename: Marika
authors.initials: M
authors.lastname: Arduin
authors.forename: Girolamo
authors.initials: G
authors.lastname: Calo
authors.forename: Martina
authors.initials: M
authors.lastname: Spagnol
authors.forename: Anna
authors.initials: A
authors.lastname: Rizzi
authors.forename: Severo
authors.initials: S
authors.lastname: Salvadori
authors.forename: Domenico
authors.initials: D
authors.lastname: Regoli
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D006801:Humans; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010456:Peptides, Cyclic / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000187:drug effects; D013329:Structure-Activity Relationship; D014579:Urotensins / Q000737:chemistry* / Q000502:physiology*
chemical_list: D010456:Peptides, Cyclic; D043562:Receptors, G-Protein-Coupled; D014579:Urotensins; C029677:urotensin II