Long polypeptide 3(10)-helices at atomic resolution.

The crystal-state preferred conformation of the terminally blocked homooctapeptide from the C(alpha,alpha)-dimethylated alpha-aminoisobutyric acid (Aib) residue, pBrBz-(Aib)(8)-OBu(t), in which pBrBz is para-bromobenzoyl and OBu(t) is tert-butoxy, determined by x-ray diffraction analysis using direct methods, was found to be a 3(10)-helix stabilized by six consecutive intramolecular N-H....O=C hydrogen bonds of the C(10)-III (or III') type. This is the first observation at atomic resolution of a regular 3(10)-helix longer than two complete turns. The solid-state structural analysis was extended to the terminally blocked, alpha-aminoisobutyric acid-rich octapeptide corresponding to the 2-9 sequence of the peptaibol antibiotics emerimicins III and IV, pBrBz-Aib(3)-L-Val-Gly-L-Leu-Aib(2)-OMe. Again, this peptide adopts a (right-handed) 3(10)-helical structure, although slightly distorted at the level of the L-leucine residue. The role of specific amino acid sequence and peptide main-chain length in stabilizing either the 3(10)- or the alpha-helical conformation and their possible implications on the nature of the channel formed by peptaibol antibiotics in the membrane are also briefly discussed.