The conformational properties of somatostatin. IV. The conformers contributing to the conformation equilibrium of somatostatin in aqueous solution as found by semi-empirical energy calculations and high-resolution NMR experiments.

The results of a conformational study by 1H and 13C high-resolution NMR at 270 and 500 MHz on the peptide hormone somatostatin have been compared with a series of conformers generated by semi-empirical energy calculations. The use of specifically deuterated phenylalanine residues has enabled us to confirm and supplement the identification of all but the phenylalanine aromatic resonances in the proton spectra of somatostatin. In order to minimize the risk of overlooking some low-energy conformations, four different strategies have been used for the generation of the conformers: two based on combinations of conformations of fragments that had been studied before, one on a random procedure and one on the conformational constraints existing in bicyclic analogs with high biological activity.

Conformational studies on somatostatin. II. The C-terminal hexapeptide fragment.

The results of a conformational study on the C terminal hexapeptide of Somatostatin are presented. Semi-empirical energy calculations and high resolution NMR methods have been used to obtain information on the conformational properties of SRIF9-14 in [2H6]dimethylsulfoxide and 2H2O. It is concluded from the energy calculations that the peptide has an averaged conformation in which semi extended and folded structures are important.

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 program for generation and selection of possible conformations of cyclic molecules.

An algorithm has been developped for the computer generation of the possible conformations of non-planar cyclic molecules. This algorithm has been used successfully to select the known conformations of the ribose ring, of substituted cyclohexane and of disulfide bridged peptides. Its use may be extended to open molecules when the end-to-end distance is known or imposed.