Aqueous self-assembly within the homologous peptide series AnK.

We compare the aqueous self-assembly behavior within the homologous peptide series AnK, where A is alanine, K is lysine, and n = 4, 6, 8, and 10. The aqueous peptide solubility, ϕ(s) (volume fraction), depends strongly on the number of hydrophobic alanine residues and decreases approximately as ϕ(s) ≈ 10(-n). Also the self-assembly structure depends on n. A4K is highly water-soluble and shows no relevant self-assembly. A6K, which has been extensively studied previously, forms hollow nanotubes in water. A8K and A10K self-assembly is characterized here using a combination of small- and wide-angle X-ray scattering, static and dynamic light scattering, cryo transmission electron microscopy, and circular dichroism spectroscopy. They both form similar thin rodlike aggregates with lengths on the order of 100 nm and a biaxial cross-section with dimensions of 4 nm × 8 nm. We show that different sample preparation protocols result in different lengths of the A10K rodlike aggregates. On the basis of these findings, the question of thermodynamic equilibrium of peptide self-assembly is discussed.

Influence of end-capping on the self-assembly of model amyloid peptide fragments.

The influence of charge and aromatic stacking interactions on the self-assembly of a series of four model amyloid peptides has been examined. The four model peptides are based on the KLVFF motif from the amyloid ß peptide, Aß(16-20) extended at the N terminus with two ß-alanine residues. We have studied NH(2)-ßAßAKLVFF-COOH (FF), NH(2)-ßAßAKLVF-COOH (F), CH(3)CONH-ßAßAKLVFF-CONH(2) (CapF), and CH(3)CONH-ßAßAKLVFF-CONH(2) (CapFF). The former two are uncapped (net charge +2) and differ by one hydrophobic phenylalanine residue; the latter two are the analogous capped peptides (net charge +1). The self-assembly characteristics of these peptides are remarkably different and strongly dependent on concentration. NMR shows a shift from carboxylate to carboxylic acid forms upon increasing concentration. Saturation transfer measurements of solvent molecules indicate selective involvement of phenylalanine residues in driving the self-assembly process of CapFF due presumably to the effect of aromatic stacking interactions. FTIR spectroscopy reveals ß-sheet features for the two peptides containing two phenylalanine residues but not the single phenylalanine residue, pointing again to the driving force for self-assembly. Circular dichroism (CD) in dilute solution reveals the polyproline II conformation, except for F which is disordered. We discuss the relationship of this observation to the significant pH shift observed for this peptide when compared the calculated value. Atomic force microscopy and cryogenic-TEM reveals the formation of twisted fibrils for CapFF, as previously also observed for FF. The influence of salt on the self-assembly of the model ß-sheet forming capped peptide CapFF was investigated by FTIR. Cryo-TEM reveals that the extent of twisting decreases with increased salt concentration, leading to the formation of flat ribbon structures. These results highlight the important role of aggregation-induced pK(a) shifts in the self-assembly of model ß-sheet peptides.

Structure of single-wall peptide nanotubes: in situ flow aligning X-ray diffraction.

The structure of single wall peptide nanotubes is presented for the model surfactant-like peptide A(6)K. Capillary flow alignment of a sample in the nematic phase at high concentration in water leads to oriented X-ray diffraction patterns. Analysis of these, accompanied by molecular dynamics simulations, suggests the favourable self-assembly of antiparallel peptide dimers into beta-sheet ribbons that wrap helically to form the nanotube wall.