| Abstract
| - Trichogin GA IV, an 11-residue lipopeptaibol blocked atthe N-terminus by an n-octanoyl group and atthe C-terminus by a 1,2-amino alcohol (l-leucinol),extracted from the fungus Trichoderma longibrachiatum,exhibitsremarkable membrane-modifying properties. We have synthesizedtrichogin GA IV and several[l-Leu-OMe11]analogs carrying at the N-terminus an acyl chain of variable length(C2−C8, C10, C12,C14, C16, C18). Asuccinoylatedhead-to-head dimer was also prepared. A conformational analysis,carried out by FTIR absorption, CD, and NMR,showed that the right-handed helical structure of the naturallipopeptaibol is essentially preserved in all its analogs.Permeability measurements revealed that at least six carbon atomsin the Nα-blocking fatty acyl moiety arerequiredfor the onset of significant membrane-modifying properties. Alsothe head-to-head dimer is remarkably active.Possible models for the mechanism of membrane permeability oftrichogin GA IV are discussed.
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