Cystine peptides. Spectroscopic studies on the conformations of a cyclic pentapeptide disulfide

The model cyclic pentapeptide disulfide Boc-Cys-Ala-Aib-Gly-Cys-NHMe 1, has been synthesized. ¹H n.m.r. studies in (CD₃)₂SO and CDCl₃-(CD₃)₂SO mixtures establish the solvent exposed nature of the Cys(l) and Aib NH groups, while a moderate degree of shielding is observed for the other four NH groups. Nuclear Overhauser effects between Cα₁H and N_i+1H protons provide evidence for extended or semi-extended conformations (ø ± 130° ± 30°) at the Cys(l), Ala(2), Gly(4) and Cys(5) residues. The n.m.r. results are supportive of an intramolecular antiparallel β-sheet conformation at these residues, nucleated by a γ-turn centered at Aib(3). This conformation is not stabilized by strong transannular hydrogen bonds. CD studies establish solvent dependent structural changes of the disulfide linkage in methanol-dioxane mixtures. An unusual CD pattern is observed for the peptide chromophore.