title: Analysis of the active conformation of angiotensin II: a comparison of AII and non-peptide AII antagonists.
abstract: Several molecular models of angiotensin II (AII) were constructed using information derived primarily from conformationally constrained AII analogues. In order to refine the original models, AII was compared using computer-aided molecular graphics with several of the recently reported non-peptide AII antagonists. As a first approximation, the imidazole, phenyl ring and acidic moiety (i.e., carboxyl, tetrazole) of the non-peptide AII antagonists were overlapped with the corresponding features of the peptide. AII and Dup 753 were overlapped using Multifit (SYBYL) and then both were optimized individually and refit; this procedure was repeated three times to generate a working model of AII. The less-potent non-peptide AII antagonists S 8308 and Exp 6155 could also be overlaid with the model of AII, albeit not as well as DuP 753. The working model of AII, which has a twisted U-shape, places the imidazole of His6 and the terminal carboxylate approximately 8.7 A apart.
authors.affiliation: Virginia Commonwealth University, Medical College of Virginia.
authors.forename: M E
authors.initials: ME
authors.lastname: Pierson
authors.forename: R J
authors.initials: RJ
authors.lastname: Freer
mesh_terms: D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000737:chemistry*; D003198:Computer Simulation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation
chemical_list: D000804:Angiotensin II