Steric Complementarity Drives Strong Co-Assembly of Short Peptide Stereoisomers

Steric complementarity plays an essential role in maintaining protein architecture and recognition. In supramolecular chemistry and material science, however, it remains a major challenge to precisely control steric complementarity and associated interactions across different length scales for the construction of higher-order peptide and protein nanostructures and nanomaterials. Through coassembly of designed aromatic short peptide stereoisomers, we here incorporate specific π-π stacking interactions into facial complementarity between peptide strands within a β-sheet in a controllable manner. The high steric complementarity between aromatic side chains leads to strong coassembly capabilities of these peptide stereoisomers and dramatic changes in supramolecular morphology and size. We also unravel suprastructural handedness codes for their coassemblies and relate them to the side chain geometric complementarity and distribution on the two faces of the β-sheet. This work not only highlights the importance of steric complementarity in peptide folding but also provides a paradigm for the fabrication of intricate peptide β-sheet assemblies via steric complementarity at the subsheet level.