Peptide conformations. 28. Relayed heteronuclear correlation spectroscopy and conformational analysis of cyclic hexapeptides containing the active sequence of somatostatin

Abstract

Homo- and heteronuclear 2-dimensional NMR techniques were used to assign the 1H and 13C NMR spectra of title cyclic peptides cyclo[Phe7-D-Trp-Lys(COCH2Ph)-Thr-X11-Pro6] [X = Gly (I), Phe (II)] in Me2SO. Unequivocal assignments of C resonances of Trp and Phe in II could only be obtained by heteronuclear relayed spectroscopy. II has a bII' turn at Phe7...Thr and a bVI turn at Thr...Phe7 including a cis peptide bond between Phe11 and Pro6. Substitution of Phe11 by Gly to give I results in a dramatic change in the conformation; 2 species of I exist in a slow equil. (70:30) in which the major isomer has a trans Gly-Pro bond. The technique of relayed heteronuclear correlation spectroscopy and an improved pulse sequence are described. [on SciFinder (R)]