Stereochemical studies on cyclic peptides. VII. Effect of different types of energies on the hydrogen-bonded conformations of cyclic hexapeptides

Abstract

A study of the conformational states of cyclic hexapeptides has been made, based on energy of conformations. Structures of cyclohexaalanyl and cyclohexaglycyl with twofold symmetry and having intracyclic 4→1 type of hydrogen bonds have been considered, taking into account hydrogen-bonding, electrostatic interactions, and torsional distortions in addition to non-bonded interaction. The results indicate that the conformation with the lowest energy is the same when the different energy factors are taken into account, both in the case of cyclohexaalanyl and in the case of cyclohexaglycyl. When the different types of conformations are compared, the effect of electrostatic interaction increases the difference in energy between the two possible different types of conformation A and B in the case of cyclohexaalanyl and A' and B in the case of cyclohexaglycyl, compared to the non-bonded contribution alone. When the hydrogen-bonding effect is included in addition to electrostatic and non-bonded van der Waals interaction, the differences are brought down and the interpretations based on this are similar to those obtained from considering non-bonded van der Waals interaction alone. Also, the most stable conformation is not the same as the one with the lowest hydrogen-bond energy alone. The torsional and bond angle distortions do not appreciably affect the relative stabilities of these conformations. The theoretical results are compared with the available experimental data.