The conformational properties of somatostatin V. Side-chain interaction in aqueous solution as studied by one-dimensional and two-dimensional NMR methods

Abstract

The occurrence of side-chain interactions in aqueous solutions of somatostatin has been studied by one- and two-dimensional proton-proton nuclear Overhauser effect NMR measurements at 500 MHz. An analysis of the aromatic region of the somatostatin spectrum is presented which demonstrates ring current shifts on the 2-phenyl protons of Phe 6 and Phe 7 not unlike the 2-phenyl proton shifts that were found in an eight amino acid analogue of somatostatin. No shifts were found for the Phe 11 ring protons. In addition, no interresidue nuclear Overhauser effects other than between Phe 6-Phe 7, Phe 7-Trp 8 and Phe 6-Trp 8 have been found at 279 and 297 K. This excludes folded structures favoured by Phe 6-Phe 11 ring interactions as a significant contributon to the conformational equilibrium at and below room temperature. The non existence of sizeable interresidue nuclear Overhauser effects can be explained by conformational averaging and unfavourable correlation times for the overall rotations as well as internal motions of the peptide. We conclude that our conformational studies on somatostatin in aqueous solution do not give conclusive evidence for ‘one’ or ‘two’ biologically active conformations.