Protected 1–3 segment of the peptaibol antibiotics alamethicin and hypelcin.

A study of the modes of folding and self-association of Z-Aib-l -Pro-Aib-OMe (the protected 1–3 segment of the peptaibol antibiotics alamethicin and hypelcin) in the solid state was performed using i.r. absorption and X-ray diffraction. The stereochemically constrained tripeptide molecules adopt a 4 ± 1 intramolecularly H-bonded form (β-turn), where the single intramolecular H-bond is found between the peptide N-H group of the Aib³ residue and the urethane C = O group of the N-blocking benzyloxycarbonyl moiety. This folded structure is stabilized by an intermolecular H-bond between the urethane N-H group of the Aib¹ residue and the peptide C = O group of the Pro² residue of a symmetry related molecule. According to the i.r. absorption data, in CH₂Cl₂ and TMP solutions the same intramolecularly H-bonded form occurs as that found in solid state. Compared to the situation in the solid state, in CH₂Cl₂ and TMP solvation of the urethane N-H group replaces self-association (through the same N-H group). The results are also discussed in relation to those obtained for other protected -Aib-X-Aib-(X = Aib, l -Ala, l -Val) tripeptide segments of peptaibol antibiotics.