title: Lipopeptaibol metabolites of tolypocladium geodes: total synthesis, preferred conformation, and membrane activity.
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=Calpha-ethylnorvaline, Aib=alpha-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 Calpha tetrasubstitution, as in the Etn-containing LP237-F8 metabolite, has a positive effect on membrane interaction.
authors.affiliation: Institute of Biomolecular Chemistry, CNR Department of Organic Chemistry, University of Padova, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Rainaldi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretto
authors.forename: Cristina
authors.initials: C
authors.lastname: Peggion
authors.forename: Fernando
authors.initials: F
authors.lastname: Formaggio
authors.forename: Stefano
authors.initials: S
authors.lastname: Mammi
authors.forename: Evaristo
authors.initials: E
authors.lastname: Peggion
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Galvez
authors.forename: Maria Dolores
authors.initials: MD
authors.lastname: Díaz-de-Villegas
authors.forename: Carlos
authors.initials: C
authors.lastname: Cativiela
authors.forename: Claudio
authors.initials: C
authors.lastname: Toniolo
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002463:Cell Membrane Permeability; D002942:Circular Dichroism; D005456:Fluorescent Dyes / Q000737:chemistry; D006860:Hydrogen Bonding; D008567:Membranes, Artificial; D003904:Mitosporic Fungi / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D054848:Peptaibols; D010455:Peptides; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D013050:Spectrometry, Fluorescence; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000900:Anti-Bacterial Agents; D005456:Fluorescent Dyes; D008567:Membranes, Artificial; D054848:Peptaibols; D010455:Peptides; D010713:Phosphatidylcholines; D010743:Phospholipids; C116937:peptaibolin