title: Design and synthesis of potent cystine-free cyclic hexapeptide agonists at the human urotensin receptor.
abstract: [structure: see text] Cyclic hexapeptides, incorporating a dipeptide unit in place of the disulfide bond found in urotensin, were prepared and screened at the human urotensin receptor. The bridging dipeptide unit was found to influence dramatically the affinity for the urotensin receptor. Alanyl-N-methylalanyl and alanylprolyl dipeptide bridges failed to afford active ligands, while the alanyl-alanyl unit yielded a ligand with submicromolar affinity for the urotensin receptor. Further development led to a hexapeptide agonist with nanomolar affinity (2.8 nM).
authors.affiliation: Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Shane
authors.initials: S
authors.lastname: Foister
authors.forename: Laurie L
authors.initials: LL
authors.lastname: Taylor
authors.forename: Jin-Jye
authors.initials: JJ
authors.lastname: Feng
authors.forename: Wen-Long
authors.initials: WL
authors.lastname: Chen
authors.forename: Atsui
authors.initials: A
authors.lastname: Lin
authors.forename: Fong-Chi
authors.initials: FC
authors.lastname: Cheng
authors.forename: Amos B
authors.initials: AB
authors.lastname: Smith
authors.forename: Ralph
authors.initials: R
authors.lastname: Hirschmann
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003553:Cystine / Q000737:chemistry; D004151:Dipeptides / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000737:chemistry*; D014579:Urotensins / Q000819:agonists* / Q000737:chemistry
chemical_list: D004151:Dipeptides; D010456:Peptides, Cyclic; D043562:Receptors, G-Protein-Coupled; C121697:UTS2R protein, human; D014579:Urotensins; D003553:Cystine