Aqueous self-assembly behaviour alteration derived from primary structure changes of model peptides

Sammanfattning: Understanding of the self-assembly behaviour of peptides is of great interest within several different areas such as neurodegenerative diseases, biotechnology, and peptide pharmaceuticals. In this work we have compared the impact on the self-assembly behaviour derived from systematic changes of the primary structure of A8K, where A denotes alanine and K lysine. Model peptides derived from A8K included in this work are KA8, G8K, and A4KA4, where G denotes glycine. In addition, we have also studied the self-assembly behaviour of binary mixtures of the model peptides to probe coaggregation of the different model peptides. To determine the aggregate structure small and wide-angle x-ray scattering and cryo TEM experiment were performed. Furthermore, to determine the secondary structure, we performed measurements using circular dichroism and infrared spectroscopy. We also probed the solubility of the model peptides through static light scattering experiments. From our results we can derive, that replacing alanine with the less hydrophobic amino acid glycine leads to a higher critical aggregation concentration, as expected. Furthermore, the change removes much of the chirality of the model peptide, leaving lysine as the only chiral amino acid in the peptide. The result from this is that G8K form two-dimensional disc-like aggregates, whereas A8K aggregates into twisted one-dimensional fibres. A higher peptide solubility is also observed for A4KA4 where the lysine amino acid has been placed in the middle of the peptide, presumably due to a destabilization of the laminated beta-sheet structure as the bulky lysine sidechain is accommodated within the peptide aggregates. By reversing the amino acids sequence, we observe a minor structural change for KA8. For the binary mixtures of A8K or KA8 and G8K, we can conclude that they coaggregate with aggregate properties reminiscent of the alanine model peptide.