Partial [alphaMe]Aun scan of [l-Leu11-OMe]-trichogin GA IV, a membrane active synthetic precursor of the natural lipopeptaibol. |
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Authors: | C Peggion V Moretto F Formaggio M Crisma C Toniolo J Kamphuis B Kaptein Q B Broxterman |
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Institution: | Biopolymer Research Center, CNR, Department of Organic Chemistry, University of Padova, Via Marzolo 1, 35131 Padua, Italy. |
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Abstract: | 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. |
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