RESUMEN
In 1953, Pauling and Corey predicted that enantiomeric ß-sheet peptides would coassemble into so-called "rippled" ß-sheets, in which the ß-sheets would consist of alternating l- and d-peptides. To date, this phenomenon has been investigated primarily with amphipathic peptide sequences composed of alternating hydrophilic and hydrophobic amino acid residues. Here, we show that enantiomers of a fragment of the amyloid-ß (Aß) peptide that does not follow this sequence pattern, amyloid-ß (16-22), readily coassembles into rippled ß-sheets. Equimolar mixtures of enantiomeric amyloid-ß (16-22) peptides assemble into supramolecular structures that exhibit distinct morphologies from those observed by self-assembly of the single enantiomer pleated ß-sheet fibrils. Formation of rippled ß-sheets composed of alternating l- and d-amyloid-ß (16-22) is confirmed by isotope-edited infrared spectroscopy and solid-state NMR spectroscopy. Sedimentation analysis reveals that rippled ß-sheet formation by l- and d-amyloid-ß (16-22) is energetically favorable relative to self-assembly into corresponding pleated ß-sheets. This work illustrates that coassembly of enantiomeric ß-sheet peptides into rippled ß-sheets is not limited to peptides with alternating hydrophobic/hydrophilic sequence patterns, but that a broader range of sequence space is available for the design and preparation of rippled ß-sheet materials.
