Controlled aggregation of peptide–DNA hybrids into amyloid-like fibrils

Abstract

We report on the fibril genesis under controlled aggregation conditions of a series of peptide–DNA hybrids composed of short peptide fragments, namely diphenylalanine (FF), ditryptophan (WW) and the amyloid β peptide motif (16–21) (KLVFFA), K stands for lysine, L for leucine, V for valine and A for alanine. The copolymers based on KLVFFA and WW form long fibers by nucleation dependent polymerization, very similar to amyloid fibril formation. At low concentrations and ambient temperature, they form spherical structures, which under controlled aggregation conditions such as increased temperature, concentration and incubation time assemble into long β-sheeted fibers, as evidenced by wide angle X-ray scattering. This mechanism is driven by π–π stacking supported by intermolecular electrostatic interactions and/or weak hydrogen bonding in an aprotic solvent such as an aqueous solution of dimethylsulfoxide (DMSO). In pure water, solely WW–DNA assembles into fibers owing to strong π–π stacking of the aromatic dipeptide stabilized by intermolecular hydrogen bonding. Overall, this study supports the mechanism of structure formation of peptide–DNA conjugates under controlled aggregation conditions.