Peptide Self-Assemblies from Unusual α-Sheet Conformations Based on Alternation of D/L Amino Acids

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 supra -molecular architectures with unique properties. In this work, we report the design of a new peptide self-assembly strategy based on unusual alpha-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-LDLLDLK-NH2 and Ac-DLLDLLDK-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 alpha-sheets instead of fi-sheets, which readily pack into tubular architectures in oligomer simulations. Simulated circular dichroism spectra based on alpha-sheet oligomers validate the proposed alpha-sheet secondary structures. These results form an important basis for the rational design of higher-order peptide assemblies with novel properties based on unusual alpha-sheet secondary structures.

Automated summary

This work reports the design of a new peptide self-assembly strategy based on unusual alpha-sheet secondary structures. Microscopic imaging, neutron scattering, and spectroscopic measurements indicate the formation of highly ordered wide nanotubes and helical ribbons by two heterochiral peptides. Molecular dynamics simulations reveal the folding of these heteropeptides into alpha-sheets, supporting the proposed secondary structures.