CONFORMATIONAL STUDIES OF ANGIOTENSIN-II AND ANALOGS IN DIMETHYL-SULFOXIDE BY H-1-NMR - LABILITY AND INTRAMOLECULAR INTERACTIONS OF THE TYROSINE HYDROXYL AND HISTIDINE IMIDAZOLE NH PROTONS

H-1 NMR studies in dimethyl sulfoxide illustrate that the tyrosine hydroxyl proton and the histidine imidazole NH proton in [Sar1]ANGII and analogues are labile at neutral pH but not at acid pH. This is attributable to intramolecular interactions of these groups with negatively charged groups. Methylation or elimination of the Tyr hydroxyl in [Sar1]ANGII and analogues, invokes a small but consistent deshielding effect on the His C-2 and C-4 protons, suggesting an interaction between the Tyr hydroxyl and the His ring. Nuclear Overhauser Effect (NOE) enhancement experiments in [Sar1]ANGII and the Sarmesin analogue [Des1,Tyr(Me)4]ANGII, support the Tyr/His interaction and confirm the presence of a trans His-Pro peptide bond.