H-1-NMR CONFORMATIONAL STUDIES IN WATER OF ANGIOTENSIN-II ANALOGS MODIFIED AT THE N-TERMINI AND C-TERMINI - INTERACTIONS OF THE AROMATIC SIDE-CHAINS AND FOLDING OF THE N-TERMINAL DOMAIN

The conformation of [Sar(1)]angiotensin II in water at neutral pH has been examined by proton magnetic resonance spectroscopy at 400 MHz and in particular by comparing its H-1 NMR spectral data with those of an alogues modified at positions 1,4 and 6, namely [Sar(1),Cha(8)]ANGII, [Des Asp(1),Cha(8)]ANGII, [Aib(1),Tyr(Me)(4)]ANGII, [Aib(1),Tyr(Me)(4) ,Ile(8)]ANGII, [N-MeAib(1),Tyr(Me)(4)]ANGII, [N-MeAib(1),Tyr(Me)(4),Il e(8)]ANGII, ANGIII and [Sar(1),Ile(8)]ANGII. Assignment of all proton resonances in these analogues was made possible by 2D COSY NMR experim ents. The H-2 and H-4 protons for the histidine ring in [Sar(1)]ANGII, ANGII and ANGIII were shielded compared with the same protons in [Sar (1),Ile(8)]ANGII, [Sar(1),Cha(8)]ANGII and [Des Asp(1),Cha(8)]ANGII; t his shielding effect was not disturbed upon methylation of the tyrosin e hydroxyl and/or replacement of residue 1 (sarcosine or aspartic acid ) with aminoisobutyric acid (Aib) or N-methyl aminoisobutyric acid (N- MeAib). These data are consistent with our previous suggestion based o n NMR studies in neutral DMSO that a characteristic folded conformatio n for ANGII previously observed in non-polar solvents can also be dete cted in water at neutral pH, but to a lesser degree.