title: Structural comparison between type I and type II antagonists: possible implications in the drug design of AT1 antagonists.
abstract: Analogues of sarilesin (type I AT1 antagonists), and sarmesin (type II AT1 antagonists) with homoserine (hSer) at position 8 were prepared and bioassayed. The presence of a Tyr4-Ile5-His6 bend found in sarmesin but not in sarilesin was identified. The obtained results coupled with conformational analysis studies, using a combination of NMR spectroscopy and computational chemistry, propose important conformational and stereoelectronic properties for agonist and antagonist activity at AT1 receptors.
authors.affiliation: Department of Chemistry, University of Patras, Greece.
authors.forename: P
authors.initials: P
authors.lastname: Roumelioti
authors.forename: T
authors.initials: T
authors.lastname: Tselios
authors.forename: K
authors.initials: K
authors.lastname: Alexopoulos
authors.forename: T
authors.initials: T
authors.lastname: Mavromoustakos
authors.forename: A
authors.initials: A
authors.lastname: Kolocouris
authors.forename: G J
authors.initials: GJ
authors.lastname: Moore
authors.forename: J M
authors.initials: JM
authors.lastname: Matsoukas
mesh_terms: D000803:Angiotensin I / Q000378:metabolism*; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D015195:Drug Design; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D051381:Rats; D011945:Receptors, Angiotensin / Q000378:metabolism; D013329:Structure-Activity Relationship; D014599:Uterus / Q000187:drug effects
chemical_list: D057911:Angiotensin Receptor Antagonists; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C040420:angiotensin II, Sar(1)-Me-Tyr(4)-; D000803:Angiotensin I