Abstract
The misfolding of proteins and peptides potentially leads to a conformation transition from an α-helix or random coil to β-sheet-rich fibril structures, which are associated with various amyloid degenerative disorders. Inhibition of the β-sheet aggregate formation and control of the structural transition could therefore attenuate the development of amyloid-associated diseases. However, the structural transitions of proteins and peptides are extraordinarily complex processes that are still not fully understood and thus challenging to manipulate. To simplify this complexity, herein, the effect of metal ions on the inhibition of amyloid-like β-sheet dipeptide self-assembly is investigated. By changing the type and ratio of the metal ion/dipeptide mixture, structural transformation is achieved from a β-sheet to a superhelix or random coil, as confirmed by experimental results and computational studies. Furthermore, the obtained supramolecular metallogel exhibits excellent in vitro DNA binding and diffusion capability due to the positive charge of the metal/dipeptide complex. This work may facilitate the understanding of the role of metal ions in inhibiting amyloid formation and broaden the future applications of supramolecular metallogels in three-dimensional (3D) DNA biochip, cell culture, and drug delivery.