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Lipopeptaibol Metabolites of Tolypocladium geodes : Total Synthesis, Preferred Conformation, and Membrane Activity
Author(s) -
Rainaldi Mario,
Moretto Alessandro,
Peggion Cristina,
Formaggio Fernando,
Mammi Stefano,
Peggion Evaristo,
Galvez José Antonio,
DíazdeVillegas Maria Dolores,
Cativiela Carlos,
Toniolo Claudio
Publication year - 2003
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200304756
Subject(s) - metabolite , chemistry , membrane , stereochemistry , amphiphile , biochemistry , organic chemistry , copolymer , polymer
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 C α tetrasubstitution, as in the Etn‐containing LP237‐F8 metabolite, has a positive effect on membrane interaction.