The crystal state conformation of Aib‐rich segments of peptaibol antibiotics

Ac‐(Aib‐Ala) 3 ‐OH (a protected segment of the peptaibols gliodeliquescin and paracelsin), Z‐Leu‐Aib‐Val‐Aib‐Gly‐O t Bu (a segment of [Leu] 7 ‐gliodeliquescin), Z‐Val‐Aib‐Aib‐Gln‐O t Bu (a common segment of alamethicin, paracelsin, and hypelcin), and Ac‐Aib‐Pro‐(Aib‐Ala) 2 ‐OMe and Z‐Aib‐Pro‐(Aib‐Ala) 2 ‐OMe, which represent differently N α ‐protected 1–6 segments of alamethicin and hypelcin, have been synthesized by solution methods. The crystal‐state conformations of these five Aib‐containing peptides have been determined by X‐ray diffraction analysis. We have confirmed that the 3 10 ‐helical structure is preferentially adopted by Aib‐rich short peptides. An experimentally unambiguous proof for the 3 10 →α‐helix conversion has been provided by the two differently N‐blocked ‐Aib‐Pro‐(Aib‐Ala) 2 ‐OMe hexapeptides. The β‐bend ribbon conformation, commonly observed in the (Aib‐Pro) n sequential oligopeptides, is not found in the ‐Aib‐Pro‐Aib‐Ala‐Aib‐Ala‐ sequence. As expected on the basis of the l ‐configuration of the C α ‐monoalkylated residues, a right‐handed helix screw sense was found in all peptides investigated. © 1998 European Peptide Society and John Wiley & Sons, Ltd.