Peptide Self‐Assembly: Insights From Functional Short Peptides, Amyloid‐β, and Gluten Peptides

In this perspective, we discuss how short peptides can be programmed through sequence design, stereochemistry, terminal modification, and external stimuli to form diverse supramolecular architectures. We then examine how similar molecular principles underlie disease-associated aggregation, focusing on early Aβ(1-42) assemblies in Alzheimer's disease and proteolysis-resistant gluten peptide nanostructures in gluten-related disorders. Attention is given to the detection, stabilization, and modulation of transient oligomeric species, which remain challenging but highly relevant to therapeutic and diagnostic targets. We further highlight how short functional peptides can be engineered to interfere with aggregation pathways in amyloid and nonamyloid aggregopathies, including diabetes-related amyloids, α-synuclein, and phenylalanine assemblies. Together, these examples illustrate the cross-applicability of concepts from supramolecular materials chemistry to molecular pathology. This perspective emphasizes that understanding peptide self-assembly at the molecular level is key to both exploiting and controlling its biological consequences.