The Intrinsic UV-Visible Fluorescence of Peptides Widely Used for Studying Amyloid Aggregation Devoid of Aromatic Residues.

Non-covalent forces are the primary drivers of biomolecular interactions. They also represent a key factor in the unexpected tendency for proteins, peptides, and even individual amino acids to self-assemble into precise supramolecular assemblies, often characterized by a β-rich, amyloid-like structure. Studies carried out in the last few decades have shown that peptides/proteins self-assembly not only has structural consequences but also generates spectroscopic properties whose origin remains debated. Here, we investigated the spectroscopic properties of four peptides, GAIIGL, NNQQ, SSTSAA, and GNNQQNG (a derivative of the frequently studied GNNQQNY peptide), devoid of aromatic residues, whose crystallographic characterization has been seminal in elucidating the basis of the aggregation process. The spectroscopic behavior of these peptides was analyzed in two different media and in the solid state, highlighting the conditions that favor UV-visible fluorescence emission. These investigations have also prompted the use of this fluorescence as a potential diagnostic tool in nanomedicine. Importantly, the identification of intrinsic fluorescence signatures in these amyloid-like assemblies may support the development of label-free optical approaches for the early detection and monitoring of aggregation-related pathological processes. For all peptides, the emitted fluorescence spans a rather wide range of wavelengths. Although centered in the blue region, a significant signal is also observed in the green region, independent of their physical state. The structural analysis of the solid used to collect the spectroscopic data reveals features related to the packings in the crystal state. This observation suggests that their three-dimensional crystal structures may serve as reliable models for studies aimed at correlating structural and spectroscopic features.