Solvent exposure of specific nuclei of angiotensin II determined by NMR solvent saturation method

CONFORMATIONAL analysis of peptides in solution by nuclear magnetic resonance (NMR) spectroscopy generally involves determination of the relative exposure to solvent of specific NH hydrogens^1-4. The four methods used so far are based on: (1) rates of NH proton exchange with labile hydrogens of the solvent^5-6; (2) temperature dependence of chemical shifts of NH resonances^7-8; (3) dependence of NH chemical shifts on the composition of a suitable solvent mixture^3,9-11, and (4) degree of resonance broadening when a paramagnetic substance is added¹². Each method has limitations. Proton exchange rates reflect not only exposure to solvent, but also proximity to functional groups of the peptide which catalyse exchange. Factors which determine the temperature dependence of NH chemical shifts are as yet poorly understood. Changes in solvent composition can alter the conformation of the peptide¹¹. Paramagnetic ions may associate preferentially with the solvent or with specific sites on the peptide.