Modulating Peptide Self-Assembly via Triblock Chiral Patterning.

The suprastructural integrity of peptide self-assemblies is driven by an intricate array of cohesive interactions that guide and maintain a hierarchical order. Seemingly minor alterations to atomic arrangement, such as substitution with D-amino acids, can dramatically affect assembly potential and resultant architecture. When a primary sequence is comprised of consecutive identical motifs, "block heterochiral" peptides can be generated by partitioning chiral inversions according to these underlying elementary units. In this work, we present a combinatorial exploration of all triblock chiral patterns for the model β-sheet-forming peptide KFE12 (Ac-(FKFE)-NH). Analysis of the four resulting enantiomer pairs reveals that each produces a unique morphology, ranging from minimal 4-nm-wide fibrils to micron-scale semi-structured aggregates. Our investigation of these variants illustrates a combination of conserved and divergent hierarchical features, reflecting complex interplay between persistent fundamental forces and the unique spatial implications of blockwise intramolecular chiral interfaces.