Peptide self-assembly is a hierarchical process during which secondary structures formed in the initial stages play a critical role in determining the subsequent assembling processes and final structural ordering. Unusual secondary structures hold promise as a source to develop novel supramolecular architectures with unique properties. In this work, we report the design of a new peptide self-assembly strategy based on unusual α-sheet secondary structures. In light of the strong propensity of leucine toward forming helical conformations and its high hydrophobicity, we design two short amphiphilic peptides Ac-L D LL D LK-NH2 and Ac- D LL D LL D K-NH2 with alternating l- and d-form amino acids. Microscopic imaging, neutron scattering, and spectroscopic measurements indicate that the two heterochiral peptides form highly ordered wide nanotubes and helical ribbons with monolayer thickness, in sharp contrast to twisted nanofibrils formed by the homochiral peptide Ac-LLLLK-NH2. Molecular dynamics simulations from monomers to trimers reveal that the two heteropeptides fold into α-sheets instead of β-sheets, which readily pack into tubular architectures in oligomer simulations. Simulated circular dichroism spectra based on α-sheet oligomers validate the proposed α-sheet secondary structures. These results form an important basis for the rational design of higher-order peptide assemblies with novel properties based on unusual α-sheet secondary structures.

We reported self-assembled core–shell nanoparticles (NPs) based on lipoprotein-like NPs and plasmid DNA (pDNA). Lipoprotein-like NPs were prepared using cholic acid (CA)-modified lipopeptides. We designed six different lipopeptides with different peptide segments to construct a series of NPs. It was proven that these NPs have different positive surface charges. These NPs could bind pDNA through electrostatic interaction to form core–shell complexes. The interactions between NPs and pDNA were systematically investigated. The number of NP charges determines the strength of the interaction between NPs and pDNA. Thus, various types of core–shell structures, such as loose and dense core–shell NPs, were found in this system. Cytotoxicity test confirmed that the carriers had no toxicity. We also proved that the core–shell structures have a good cell transfection effect. This study would expand the application of lipopeptide assemblies in the gene delivery field, which may lead to the development of peptide-based gene vectors for therapeutic application.

Surfactant-like short peptides are a kind of ideal model for the study of chiral self-assembly. At present, there are few studies on the chiral self-assembly of multicharged surfactant-like peptides. In this study, we adopted a series of short peptides of Ac-I4KGK-NH2 with different combinations of L-lysine and D-lysine residues as the model molecules. TEM, AFM and SANS results showed that Ac-I4 L KG L K-NH2, Ac-I4 L KG D K-NH2, and Ac-I4 D KG L K-NH2 formed the morphologies of nanofibers, and Ac-I4 D KG D K-NH2 formed nanoribbons. All the self-assembled nanofibers, including the intermediate nanofibers of Ac-I4 D KG D K-NH2 nanoribbons, showed the chirality of left handedness. Based on the molecular simulation results, it has been demonstrated that the supramolecular chirality was directly dictated by the orientation of single β strand. The insertion of glycine residue demolished the effect of lysine residues on the single strand conformation due to its high conformational flexibility. The replacement of L-isoleucine with Da-isoleucine also confirmed that the isoleucine residues involved in the β-sheet determined the supramolecular handedness. This study provides a profound mechanism of the chiral self-assembly of short peptides. We hope that it will improve the regulation of chiral molecular self-assembly with achiral glycine, as well.