Stereoselective Coassembly of Chiral Isomer Peptide Pairs.

Peptide coassembly and self-assembly are complex processes that enable the formation of intricate nanoscale structures, facilitating the development of novel functional biomaterials. In this study, we explore stereocomplexation-driven enantiomeric coassembly, focusing on the distinctive structures of 'block heterochiral' peptides. Using the model amphipathic peptide KFE8 (FKFEFKFE), which consists of two FKFE blocks, we created homochiral peptides made of repeat units with the same chirality (LL and DD) or heterochiral variants with opposite chirality units (LD and DL). We examined the pairwise assembly behaviors of these identical peptides, which differ only in segmented stereoisomerization. We analyzed the nano-, micro-, and macroscale properties of LL/LD, LL/DL, DD/LD, and DD/DL, each representing two equimolar stereoisomers mixed before solubilization ('premixed') to enable potential coassembly or self-sorting within a single, well-mixed monomer phase. We also used 'postmixed systems', which were assembled separately and combined only before data collection for each technique (e.g., LL+LD) as controls. Our data show that homochiral or heterochiral peptide pairs with matching N-terminal chirality coassemble, while a mismatch in N-terminal chirality promotes self-sorting behavior.