title: Short pseudopeptides containing turn scaffolds with high AT2 receptor affinity.
abstract: Two pentapeptides, Ac-Tyr-Ile-His-Pro-Phe/Ile, were synthesized and shown to have angiotensin II AT2 receptor affinity and agonistic activity. Based on these peptides, a new series of 13 pseudopeptides was synthesized via introduction of five different turn scaffolds replacing the Tyr-Ile amino acid residues. Pharmacological evaluation disclosed subnanomolar affinities for some of these compounds at the AT2 receptor. Substitution of Phe by Ile in this series of ligands enhanced the AT2 receptor affinity of all compounds. These results suggest that the C-terminal amino acid residues can be elaborated on to enhance the AT2 receptor affinity in truncated Ang II analogues.
authors.affiliation: Department of Medicinal Chemistry, Division of Organic Pharmaceutical Chemistry, Uppsala University, PO Box 574, SE-751 23 Uppsala, Sweden.
authors.forename: Jennie
authors.initials: J
authors.lastname: Georgsson
authors.forename: Ulrika
authors.initials: U
authors.lastname: Rosenström
authors.forename: Charlotta
authors.initials: C
authors.lastname: Wallinder
authors.forename: Hélène
authors.initials: H
authors.lastname: Beaudry
authors.forename: Bianca
authors.initials: B
authors.lastname: Plouffe
authors.forename: Gunnar
authors.initials: G
authors.lastname: Lindeberg
authors.forename: Milad
authors.initials: M
authors.lastname: Botros
authors.forename: Fred
authors.initials: F
authors.lastname: Nyberg
authors.forename: Anders
authors.initials: A
authors.lastname: Karlén
authors.forename: Nicole
authors.initials: N
authors.lastname: Gallo-Payet
authors.forename: Anders
authors.initials: A
authors.lastname: Hallberg
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D008099:Liver / Q000378:metabolism; D008956:Models, Chemical; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009215:Myometrium / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000737:chemistry / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D013552:Swine
chemical_list: D010455:Peptides; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2