Synthesis of a 19-residue peptide with alamethicin-like activity.

Abstract

This The peptide also affects the electrical properties of planar artificial lipid membranes in a unique and specific way: minute concentrations of ALA induce voltage-dependent conductances that mimic the action potential phenomena observed in nerve membranes. These effects were observed by Mueller and Rudin (6) and have been studied also by other groups (7-9). It is now generally believed that several ALA molecules aggregate in the membrane to form ion-conducting channels (8,(10)(11)(12).Despite a number of physicochemical (13, 14), conformational (15-18), and chemical (17-22) studies, the primary structure of ALA remains unknown. Currently, there are two proposed sequences: a cyclic (ALA-c) and an open chain (ALA-o) peptide structure (Fig. 1). The former, proposed by Payne et al. (19), has been confirmed by Ovchinnikov et al. (20), while the latter, proposed by Martin and Williams (21,22), found the support of the Jung group (17). The two proposals agree on a sequence of 15 consecutive residues (3-17 according to ALA-o numbering). In ALA-c the y-carboxyl group of Glu'8 is in amide linkage with Pro2 to form a cyclic structure. In

Structural and dipolar properties of the voltage-dependent pore former alamethicin in octanol/dioxane

“…Finally we report that the ultracentrifugation work in pure octanol yielded a weight-average molecular weight of 2,700 using a partial volume of v = 0.80 ml/g (as determined from pertinent density measurements). The molecular weight of an alamethicin monomer is 1,962, as can be computed on the basis of its chemical composition (6). Therefore the peptide must be predominantly monomeric in octanol with only some minor portion of dimers and/or larger aggregates.…”

“…Alamethicin seems to be specially well suited to be studied in this way. Its primary structure has been elucidated as being a certain linear sequence of 19 amino acids (6). From circular-dichroism spectra, pronounced changes of molecular conformation are indicated depending on the lipophilicity of the solvent (7).…”

Quest for the chemical synthesis of proteins

“…He succeeded, e.g. in the solid-phase synthesis of alamethicin or valinomycin [30,31]. These examples clearly show that the stage was set for the quest to chemically synthesize biologically active proteins.…”

Micro- and macrokinetic behavior of the subunit gating channel

“…One such molecular interpretation derives from measured properties of molecules that are known to form channels and/or induce electrical excitability in lipid bilayers (Martin & Williams, 1976;Gisin, Kobayashi & Hall, 1977;Yantorno, Takashima & Mueller, 1977). A channel subunit molecule is postulated to have special structural, amphiphilic, and electrical properties.…”