Cis/trans conformational equilibrium across the N-methylphenylalanine- N-methylphenylalanine peptide bond of arginine vasopressin analogs.

Two cyclic analogs of vasopressin, -Pro-Arg-Gly-NH(2) (1) and -Pro-Arg-Gly-NH(2) (2) were synthesized by the solid phase method. Their structure was determined in aqueous solution by two-dimensional NMR techniques and simulated annealing algorithm from an extended template in X-PLOR. The total chemical shift correlation spectroscopy and rotating-frame Overhauser enhancement spectroscopy of the peptides displayed four distinct sets of residual proton resonances. This suggests that both analogs adopt four families of conformations in H(2)O/D(2)O (9 : 1) (one major and three minor species). In further analysis only signals of major species (M) and of one minor species (m(1)) were considered. The major species of both peptides include a trans peptide bond between the first and second residue, and a cis form between the second and third residue. In the minor species, all peptide bonds were found to exist in trans geometry.