title: Synthesis of a new class of druglike angiotensin II C-terminal mimics with affinity for the AT2 receptor.
abstract: Four tripeptides corresponding to the C-terminal region of angiotensin II were synthesized. One of these peptides (Ac-His-Pro-Ile) showed moderate binding affinity for the AT2 receptor. Two aromatic histidine-related scaffolds were synthesized and introduced in the tripeptides to give eight new peptidomimetic structures. Three of the new peptide-derived druglike molecules exhibited selective, nanomolar affinity for the AT2 receptor. These ligands may become lead compounds in the future development of novel classes of selective AT2 receptor agonists.
authors.affiliation: Department of Medicinal Chemistry, Division of Organic Pharmaceutical Chemistry, BMC, Uppsala University, P.O. Box 574, SE-751 23 Uppsala, Sweden.
authors.forename: Jennie
authors.initials: J
authors.lastname: Georgsson
authors.forename: Christian
authors.initials: C
authors.lastname: Sköld
authors.forename: Milad
authors.initials: M
authors.lastname: Botros
authors.forename: Gunnar
authors.initials: G
authors.lastname: Lindeberg
authors.forename: Fred
authors.initials: F
authors.lastname: Nyberg
authors.forename: Anders
authors.initials: A
authors.lastname: Karlén
authors.forename: Anders
authors.initials: A
authors.lastname: Hallberg
authors.forename: Mats
authors.initials: M
authors.lastname: Larhed
mesh_terms: D000804:Angiotensin II / Q000737:chemistry*; D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D008024:Ligands; D008099:Liver / Q000378:metabolism; D008958:Models, Molecular; D018716:Molecular Mimicry; D009215:Myometrium / Q000378:metabolism; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D044139:Receptor, Angiotensin, Type 2 / Q000819:agonists*; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: D008024:Ligands; D009842:Oligopeptides; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II