We have synthesized by solution methods and characterized the lipopeptaibol metabolite LP237-F8 extracted from the fungus Tolypocladium geodes and five selected analogues with the Etn→Aib or Etn→Nva replacement at position 8 and/or a triple Gln→Glu(OMe) replacement at positions 5, 6, and 9 (Etn=Cα-ethylnorvaline, Aib=α-aminoisobutyric acid, Nva=norvaline). Conformation analysis, performed by FT-IR absorption, NMR, and CD techniques, strongly supports the view that the six terminally blocked decapeptides are highly helical in solution. Helix topology and amphiphilic character are responsible for their remarkable membrane activity. At position 8 the combination of high hydrophobicity and Cα tetrasubstitution, as in the Etn-containing LP237-F8 metabolite, has a positive effect on membrane interaction.
Preferred Conformation and Membrane Activity of the LP237-F Lipopeptaibols
RAINALDI, MARIO;MORETTO, ALESSANDRO;PEGGION, CRISTINA;FORMAGGIO, FERNANDO;MAMMI, STEFANO;PEGGION, EVARISTO;TONIOLO, CLAUDIO
2002
Abstract
We have synthesized by solution methods and characterized the lipopeptaibol metabolite LP237-F8 extracted from the fungus Tolypocladium geodes and five selected analogues with the Etn→Aib or Etn→Nva replacement at position 8 and/or a triple Gln→Glu(OMe) replacement at positions 5, 6, and 9 (Etn=Cα-ethylnorvaline, Aib=α-aminoisobutyric acid, Nva=norvaline). Conformation analysis, performed by FT-IR absorption, NMR, and CD techniques, strongly supports the view that the six terminally blocked decapeptides are highly helical in solution. Helix topology and amphiphilic character are responsible for their remarkable membrane activity. At position 8 the combination of high hydrophobicity and Cα tetrasubstitution, as in the Etn-containing LP237-F8 metabolite, has a positive effect on membrane interaction.
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