title: A frame shifted disulfide bridged analogue of angiotensin II.
abstract: N-(2-Mercaptoethyl)glycine [NMGly] was incorporated into the 3 and 5 positions of angiotensin II and oxidized to give the corresponding cyclized disulfide c[NMGly(3,5)]Ang II. The binding affinity to the angiotensin II receptor (AT(1)) of this conformationally constrained analogue, which is related to the potent Ang II agonist c[Hcy(3,5)]Ang II, was examined. The analogue had no affinity to the AT(1) receptor. Theoretical conformational analysis was performed to compare the conformational characteristics of model compounds of c[Hcy(3,5)]Ang II and the frame shifted analogue c[NMGly(3,5)]Ang II in an attempt to explain the lack of affinity.
authors.affiliation: TU Darmstadt, Institut for Organic Chemistry, Petersenstr. 22, D-64287 Darmstadt, Germany. schimbo@oc.chemie.tu.darmstadt.de
authors.forename: Boris
authors.initials: B
authors.lastname: Schmidt
authors.forename: Christian
authors.initials: C
authors.lastname: Kühn
authors.forename: Dennis K
authors.initials: DK
authors.lastname: Ehlert
authors.forename: Gunnar
authors.initials: G
authors.lastname: Lindeberg
authors.forename: Susanna
authors.initials: S
authors.lastname: Lindman
authors.forename: Anders
authors.initials: A
authors.lastname: Karlén
authors.forename: Anders
authors.initials: A
authors.lastname: Hallberg
mesh_terms: D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D002455:Cell Division / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006224:Cricetinae; D004220:Disulfides / Q000737:chemistry*; D007202:Indicators and Reagents; D010455:Peptides / Q000138:chemical synthesis; D011487:Protein Conformation; D011869:Radioligand Assay; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000378:metabolism
chemical_list: D004220:Disulfides; D007202:Indicators and Reagents; D010455:Peptides; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II