Supramolecular β-sheet peptide nanomaterials are of critical interest due to their relevance in amyloid disorders and are increasingly valued for applications in regenerative medicine, tissue engineering, and antimicrobial design. Amphipathic peptides, particularly those with alternating hydrophobic and hydrophilic residues, readily form amyloid-like pleated β-sheet fibrils. It has been demonstrated that the amino acid sequence order of isomeric peptides dramatically influences the self-assembly propensity of the resulting sequences as well as the morphology of the assembled pleated β-sheet nanomaterials. This was substantiated by our previous investigations of the peptides Ac-(FKFE)2-NH2 (L1), Ac-(FK)2(FE)2-NH2 (L2), Ac-KE(F)4KE-NH2 (L3), Ac-(KFFE)2-NH2 (L4), and Ac-FF(KE)2FF-NH2 (L5). Recently, interest in the Pauling and Corey rippled β-sheet motif, composed of coassembled enantiomeric l- and d-peptides in which the l- and d-enantiomers are organized in an alternating fashion, has been revitalized, although understanding of the rippled β-sheet fold lags far behind that of the naturally occurring pleated β-sheet. Herein, we interrogate the scope of rippled β-sheet formation by extending our previous study of the L1-L5 peptides to enantiomeric mixtures of these sequences to understand the effect of sequence order on rippled β-sheet formation. These integrated experimental and computational studies confirm that enantiomeric mixtures of these peptides have a significantly higher propensity to coassemble into putative rippled β-sheets than single enantiomers have to self-assemble into pleated β-sheets under the same solvent and concentration conditions. These findings extend our understanding of the rippled β-sheet motif and highlight the potential to exploit stereochemically diverse peptides in the design of next-generation biomaterials.
Jones et al. (Fri,) studied this question.