Broadband terahertz signatures and vibrations of Phe-Phe peptide and its fibrils.

In recent years, peptide-based nanomaterials gain significant attention in drug discovery due to their promising functionality in biophysical processes and low production costs. Among synthetic short peptides, diphenylalanine (Phe-Phe), a templating block in amyloid fibrils, shows notable self-assembling properties and potential applications in drug delivery and nanostructured biomaterials with interesting functional peculiarities and biocompatibility. Conformational flexibility at ps timescale shapes biomolecules-ligands interactions and represents a useful tool to directly probe biocompatibility and functionality of nanostructured materials. We highlight here the Terahertz (THz) fingerprint of Phe-Phe, demonstrating that several intramolecular and intermolecular ps modes occur between 0.2 and 4 THz. Through the combination of experimental and computational approaches, we get valuable insights into two different assembled forms of Phe-Phe as crystalline commercial powder and after inducing fibrillar self-assembly. Phe-Phe shows a refractive index of about 1.47, and several THz vibrations, belonging to torsions and bending of the intramolecular structure, detect at 0.55, 0.83, 1.13, 1.40, 1.68, 2.18, 2.71, 3.00, and 3.33 THz. Moreover, the observation of a mode at 1.8 THz, assign to intermolecular vibrations, highlights the impact of THz spectroscopy in detecting different assembly states of Phe-Phe.