Circular dichroism studies of ampullosporin-A analogues

• Published in: Journal of peptide science Vol. 9; no. 11-12; pp. 714 - 728
• Main Authors: Nguyen, Hoai-Huong, Imhof, Diana, Kronen, Matthias, Gräfe, Udo, Reissmann, Siegmund
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.11.2003
• Subjects: Amino Acid Sequence; Cell Membrane Permeability; Circular Dichroism; conformational study; Detergents - pharmacology; Fungal Proteins - chemical synthesis; Fungal Proteins - chemistry; Models, Biological; peptaibol; Peptides - chemical synthesis; Peptides - chemistry; Phoma; Protein Structure, Secondary - drug effects; Solvents - pharmacology; Structure-Activity Relationship; Temperature
• ISSN: 1075-2617; 1099-1387
• DOI: 10.1002/psc.459

Ampullosporin A (AmpA), a 15mer peptaibol containing seven Aib residues is able to induce pigmentation on Phoma destructiva and hypothermia in mice, as well as to exhibit a neuroleptic effect. A circular dichroism study of ampullosporin A and its analogues was carried out in organic solvents with different polarities and detergent micelles to determine the relationship between their conformational flexibility and biological activities. The analogues were obtained by modifying the N‐ and C‐termini of ampullosporin A. Furthermore, Gln and Leu were systematically substituted by Ala and Aib residues were replaced by Ala and/or Ac6c. To estimate the helicity of the analogues, the CD spectrum of AmpA recorded in acetonitrile was correlated to its crystal structure. All analogues displayed similar CD curve shapes in organic solvents with the ratio between two negative band intensities R = [θ]n−π*/[θ]π−π* < 1. In acetonitrile, most of the analogues adopted a 70%–85% helical structure, which was higher than the average of 40%–60% obtained in TFE. In detergent micelles, the analogues were distinguishable by their CD profiles. For most of the biologically active analogues, the CD spectra in detergent micelles were characterized by a R ratio > 1 and increased helicity compared with those recorded in TFE, suggesting that the interaction of the peptides with the membrane and peptide association was necessary for their hypothermic effect. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd.