Partial [alphaMe]Aun scan of [l-Leu11-OMe]-trichogin GA IV, a membrane active synthetic precursor of the natural lipopeptaibol.
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 Calpha,alpha-disubstituted glycine l-(alphaMe)Aun, respectively [partial (alphaMe)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 Nalpha-acetylated l-(alphaMe)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 Nalpha-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.
Peggion
C
C
Biopolymer Research Center, CNR, Department of Organic Chemistry, University of Padova, Via Marzolo 1, 35131 Padua, Italy.
Moretto
V
V
Formaggio
F
F
Crisma
M
M
Toniolo
C
C
Kamphuis
J
J
Kaptein
B
B
Broxterman
Q B
QB
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry*; D002942:Circular Dichroism; D006020:Glycopeptides; D006838:Hydrocarbons / Q000737:chemistry*; D055666:Lipopeptides; D008074:Lipoproteins / Q000737:chemistry*; D008566:Membranes / Q000737:chemistry; D008968:Molecular Conformation; D010455:Peptides; D012996:Solutions / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013501:Surface-Active Agents / Q000138:chemical synthesis; D014867:Water / Q000737:chemistry
D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D006838:Hydrocarbons; D055666:Lipopeptides; D008074:Lipoproteins; D010455:Peptides; D012996:Solutions; D013501:Surface-Active Agents; C116419:trichogin GA IV; D014867:Water