Partial [αMe]Aun scan of [l-Leu11-OMe]-trichogin GA IV, a membrane active synthetic precursor of the natural lipopeptaibol

• Published in: The journal of peptide research 2001-10, Vol.58 (4), p.317-324
• Main Authors: Peggion, C., Moretto, V., Formaggio, F., Crisma, M., Toniolo, C., Kamphuis, J., Kaptein, B., Broxterman, Q.B.
• Format: Article
• Language: English
• Subjects: amphiphilic peptide; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Circular Dichroism; Glycopeptides; Hydrocarbons - chemistry; infrared absorption; lipopeptaibol; Lipopeptides; Lipoproteins - chemistry; membrane mimetic environment; Membranes - chemistry; Molecular Conformation; Peptides; Solutions - chemistry; Spectroscopy, Fourier Transform Infrared; Surface-Active Agents - chemical synthesis; Water - chemistry; α-helix
• ISSN: 1397-002X; 1399-3011
• DOI: 10.1034/j.1399-3011.2001.00919.x

: We synthesized using solution‐phase methods three analogs of [l‐Leu11‐OMe] trichogin GA IV, a membrane active synthetic precursor of the lipopeptaibol antibiotic in which the N‐terminal n‐octanoyl group and each of the three Aib residues in positions 1, 4 and 8 are replaced by an acetyl group and the lipophilic Cα,α‐disubstituted glycine l‐(αMe)Aun, respectively [partial (αMe)Aun scan]. FT‐IR absorption and CD analyses unequivocally show that the main three‐dimensional structural features of [l‐Leu11‐OMe] trichogin GA IV are preserved in the analogs. Also, [l‐Leu11‐OMe] trichogin GA IV and the three Nα‐acetylated l‐(αMe)Aun analogs exhibit strictly comparable membrane‐modifying properties. Taken together, these results strongly favor the conclusion that a shift of the long hydrocarbon moiety from the Nα‐blocking group to the side‐chain of the 1, 4 or 8 residue does not have any significant effect on the conformational properties or the membrane activity of [l‐Leu11‐OMe] trichogin GA IV and, by extension, of the natural lipopeptaibol.