title: Role of the NH2-terminal domain of angiotensin II (ANG II) and [Sar1]angiotensin II on conformation and activity. NMR evidence for aromatic ring clustering and peptide backbone folding compared with [des-1,2,3]angiotensin II.
abstract: The role of the NH2 termini of angiotensin II (ANG II) and [Sar1]ANG II on conformation and activity were examined by proton NMR two-dimensional-J-correlated spectroscopy and one-dimensional nuclear Overhauser effect studies in the relatively nonpolar "receptor-simulating" environment provided by dimethyl sulfoxide-d6, using the biologically inactive COOH-terminal pentapeptide [des1,2,3]ANG II as control. Irradiation of C alpha H, C2H, and C4H proton resonances in ANG II and [Sar1]ANG II resulted in enhancements of Tyr and Phe ring proton resonances, indicating that the three aromatic rings cluster together. Very strong enhancements (17-22%) of the C alpha Y proton resonance in ANG II and [Sar1]ANG II upon irradiation of the C alpha H proton resonance, and vice versa, revealed that a Tyr-Ile-His bend is a predominant feature of the conformation of the two agonists. In contrast, saturation of the C alpha H and C alpha Y proton resonances in the control pentapeptide [des-1,2,3]ANG II did not produce, respectively, any C alpha Y or C alpha H proton nuclear Overhauser effect enhancement, illustrating the absence of a Tyr-Ile-His bend in the truncated ANG II peptide. The present findings indicate that the NH2-terminal domain of ANG II appears to have an essential role in generating the biologically active charge relay conformation of the hormone.
authors.affiliation: Department of Chemistry, University of Patras, Greece.
authors.forename: J M
authors.initials: JM
authors.lastname: Matsoukas
authors.forename: J
authors.initials: J
authors.lastname: Hondrelis
authors.forename: M
authors.initials: M
authors.lastname: Keramida
authors.forename: T
authors.initials: T
authors.lastname: Mavromoustakos
authors.forename: A
authors.initials: A
authors.lastname: Makriyannis
authors.forename: R
authors.initials: R
authors.lastname: Yamdagni
authors.forename: Q
authors.initials: Q
authors.lastname: Wu
authors.forename: G J
authors.initials: GJ
authors.lastname: Moore
mesh_terms: D000465:Algorithms; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000737:chemistry*; D000809:Angiotensins / Q000737:chemistry*; D004121:Dimethyl Sulfoxide; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry*; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D000809:Angiotensins; D010446:Peptide Fragments; D000804:Angiotensin II; C022782:angiotensin pentapeptide; C074793:angiotensin II, Sar(1)-; D004121:Dimethyl Sulfoxide