Sequence shuffle controls morphological consequences in a self-assembling tetrapeptide.

Peptide and protein self-assembly is a well-studied phenomenon in chemistry and biology, where nanoscopic building blocks exhibit rapid self-association to reveal supramolecular aggregates of defined structural features. These superstructures are stabilized by hydrophobic interactions, hydrogen bonding and a host of other noncovalent interactions. Thus, amino acid side chains in the primary structure hold importance in dictating secondary structures and preference for particular conformational signatures in peptide aggregates. This report describes contrasting nanoscale morphologies in antamanide-derived synthetic tetrapeptide mutants, which are composed by shuffling only two amino acids: phenylalanine and proline. Remarkable differences in ultrastructures in primary sequence-shuffled tetrapeptides suggest dissimilar aggregational pathways due to context-dependent location of proline and phenylalanine residues with respect to one another.