The conformational equilibria of a renin inhibitor peptide in solution

Abstract

The conformational equilibrium of a decapeptide renin inhibitory Peptide (RIP), NHPHPFHFFVYKCO 2H) in water, methanol and trifluoroethanol has beeen investigated. The value of a combined spectroscopic approach was apparent, with the need to define conformational states that were mixtures of conformational forms. Similarities between this study and that of the Melanin Concentrating Hormone (MCH) core peptide (5–14) are notable [1]. In water, two β-turn conformations and an extended form were found to be in equilibrium, with cis/trans isomerism at Pro-3. Extended conformations associated with the P II helix and irregular forms were more favoured in aqueous environments. In MeOH and TFE, two β-turn conformations associated with overlapping sequences and cis/trans isomerism at Pro-3 amide bond were seen to be in equilibrium. 2D ROESY and chemical-exchange cross-peaks were detected by 1H NMR and used to build up detailed models of the interconverting β-turn conformations of RIP.