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

Ac-(Aib-Ala)(3)-OH (a protected segment of the peptaibols gliodeliquescin a nd paracelsin), Z-Leu-Aib-Val-Aib-Gly-OtBu (a segment of [Leu](7)-gliodeliq uescin), Z-Val-Aib-Aib-Gln-OtBu (a common segment of alamethicin, paracelsi n, and hypelcin), and Ac-Aib-Pro-(Aib-Ala)(2)-OMe and Z-Aib-Pro-(Aib-Ala)(2 )-OMe, which represent differently N-alpha-protected 1-6 segments of alamet hicin and hypelcin, have been synthesized by solution methods. The crystal- state conformations of these five Aib-containing peptides have been determi ned by X-ray diffraction analysis. We have confirmed that the 3(10)-helical structure is preferentially adopted by Aib-rich short peptides. An experim entally unambiguous proof for the 3(10)-->alpha-helix conversion has been p rovided by the two differently N-blocked -Aib-Pro-(Aib-Ala)(2)-OMe hexapept ides. The beta-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-alpha-m onoalkylated residues, a right-handed helix screw sense was found in all pe ptides investigated. (C) 1998 European Peptide Society and John Wiley & Son s, Ltd.