Lipopeptaibol metabolites of tolypocladium geodes: total synthesis, preferred conformation, and membrane activity.
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.
Rainaldi
Mario
M
Institute of Biomolecular Chemistry, CNR Department of Organic Chemistry, University of Padova, Italy.
Moretto
Alessandro
A
Peggion
Cristina
C
Formaggio
Fernando
F
Mammi
Stefano
S
Peggion
Evaristo
E
Galvez
José Antonio
JA
Díaz-de-Villegas
Maria Dolores
MD
Cativiela
Carlos
C
Toniolo
Claudio
C
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
D000900:Anti-Bacterial Agents; D005456:Fluorescent Dyes; D008567:Membranes, Artificial; D054848:Peptaibols; D010455:Peptides; D010713:Phosphatidylcholines; D010743:Phospholipids; C116937:peptaibolin