Stereochemical studies on cyclic peptides. V. Conformational analysis of cyclohexapeptides

Abstract

A conformational study of cyclohexapeptides with alanyl and glycyl residues has been made based on stereochemical criteria and from potential energy considerations. Two types of structures have been considered (A) those having sixfold symmetry and (B) those with twofold symmetry and an internal hydrogen bond. The sixfold symmetrical structure showed minimum energy for the conformations (15°, 118°, 54°, 131°) and (12°, 112°, 104°, 91°) corresponding to (ω, τ, π,φ) for alanyl and glycyl residues respectively. Energetically more favourable hydrogen-bonded structures are found to be possible for twofold symmetrical cyclic hexapeptides. The conformations with the parameters (111°, 24°, 352°), (110°, 120°, 290°), (110°, 240°, 210°) and (109°, 276°, 111°), (110°, 130°, 290°), (110°, 230°, 220°) corresponding to (τ₁, π₂φ₁), (τ₂, π₂, φ₂), (τ₃, π₃, φ₃) have been found to have minimum energies for alanyl and glycyl compounds respectively. The present study shows that the minimum energy conformation is dependent on the potential energy function used in the case of cyclohexaalanyl. A comparison of the results with those of the two observed structures cyclohexaglycyl hemihydrate and ferrichrome A tetrahydrate shows that whereas there is good agreement with the latter, this is not quite so with the former.