Molecular shape and dipole moment of alamethicin-like synthetic peptides.

The peptides Boc-(L-Ala-Aib-L-Ala-Aib-L-Ala)n-OMe, with n = 2 (P10) and n = 4 (P20), have been synthesized as purely hydrophobic models of the antibiotic alamethicin, which is known to be a voltage-dependent pore former in membranes and is apparently alpha-helical in lipophilic media. These peptides were investigated in 1-octanol, a solvent which resembles the membrane environment. From dielectric dispersion studies quantitative information on the molecular shape and dipole moments could be derived. Further independent data concerning conformation and extent of aggregation of the peptides were obtained by circular dichroism and ultracentrifuge measurements. The results suggest that the peptides assume the form of elongated particles having a significant amount of ordered secondary structure and carrying a dipole parallel to the long axis. Apparently the monomeric peptide molecules undergo, to some extent, a head-to-tail aggregation which is slightly enhanced at lower temperatures. Based on the high-frequency parts of the dielectric dispersion curves the lengths, diameters, and dipole moments of the monomer particles have been determined as 22.5A, 10A, 36 D (P10) and 28.5A, 12A, 64D (P20).