CONFORMATIONAL PROPERTIES OF SOME FRAGMENTS OF THE PEPTIDE-HORMONE SOMATOSTATIN

The conformational properties of some somatostatin fragments were studied using high resolution NMR and semi-empirical calculations. The fragments were 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 solvants, combined with a new method for determining dihedral angles .vphi. and .psi. from 13C and 1H spin lattice relaxation times were presented. A marked inequivalence of the 2 Thr10,12 residues was attributed to a shielding of the Thr10 side chain by the Phe11 aromatic ring. The calculations showed the existence of extended and folded low energy conformations in the tri- and tetrapeptide. Only the folded structures gave the observed shielding of Thr10. A temperature study of the tri- and tetrapeptide indicated that the folded structures are energetically the most favorable conformations at room temperature in dimethylsulfoxide. Increasing temperature reduced the nonequivalence of the Thr residues towards the differences that were observed in 2H2O. A detailed comparison of 3J.alpha.NH coupling constants and relaxation time measurements with the calculated conformations was in general good agreement between both approaches. In these linear peptides, although several quite different low energy conformations exist, some of them are predominant. The continuity of 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.