Influence of the secondary structure on the pore forming properties of synthetic alamethicin analogs: NMR and molecular modelling studies.
Synthetic alamethicin analogs, in which all Aib residues had been replaced by Leu (L2) then proline 14 replaced by an alanine (L5), were studied in SDS micelles using circular dichroism and NMR spectroscopy. Nuclear Overhauser effects were used as constraints for molecular modelling. The structures determined for both peptides in SDS micelles were compared with those previously obtained in methanol in order to establish a secondary structure/ionophore activity relationship. Our results indicated that a shortening of peptide helices could be responsible for the observed decrease in ion channel lifetimes. However, the length of helices may not by itself explain the drastic destabilization of channels when Pro14 of alamethicin is replaced by Ala in L5. Indeed analysis of the helical wheel of L5 reveals heterogeneity in the amphipathicity depending on the medium. Thus, loss of amphipathicity seems to underly the observed destabilization of channels.
Brachais
L
L
UMR 6522 CNRS, IFRMP 23, Faculté des Sciences de Rouen, Université de Rouen, Mont Saint Aignan, France.
Mayer
C
C
Davoust
D
D
Molle
G
G
D000408:Alamethicin / Q000031:analogs & derivatives* / Q000737:chemistry*; D000595:Amino Acid Sequence; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018272:Porins / Q000737:chemistry; D017510:Protein Folding; D017433:Protein Structure, Secondary
D018272:Porins; D000408:Alamethicin