The conformational properties of some fragments of the peptide hormone somatostatin.

The conformational properties of some somatostatin fragments have been studied using high resolution NMR and semi-empirical calculations. The fragments are Thr10-Phe11, Phe11-Thr12, Thr10-Phe11-Thr12 and Thr10-Phe11-Thr12-Ser13. The results of high resolution 1H and 13C NMR using dimethylsulfoxide and 2H2O as solvents, combined with a new method for determining dihedral angles phi and psi from 13C and 1H spin lattice relaxation times are presented. A marked inequivalence of the two Thr10,12 residues is attributed to a shielding of the the Thr10 side chain by the Phe11 aromatic ring. The calculations show the existence of extended and folded low energy conformations in the tri and tetrapeptide. Only the folded structures give the observed shielding of Thr10. A temperature study of the tri and the tetrapeptide indicates that the folded structures are energetically the most favorable conformations at room temperature in dimethylsulfoxide. Increasing temperature reduces the nonequivalence of the Thr residues towards the differences that are observed in 2H2O. A detailed comparison of 3JalphaNH coupling constants and relaxation time measurements with the calculated conformations gives in general good agreement between both approaches. It is concluded that in these linear peptides, although several quite different low energy conformations exist, some of them are predominant. The continuity of both NMR parameters and calculated low energy conformations, when going from the smaller to the larger peptides, demonstrates the existence of structural properties far from the "random conformation".