Amyloid-Like Fibrillary Morphology Originated by Tyrosine-Containing Aromatic Hexapeptides

Phenylalanine-based nanostructures have attracted the attention of the material science community for their functional properties. These properties strongly depend on the hierarchic organization of the nanostructure that in turn can be finely tuned by punctual chemical modifications of the building blocks. Herein, we investigate how the partial or the complete replacement of the Phe residues in PEG₈-(Phe)₆ (PEG₈-F6) with tyrosines to generate PEG₈-(Phe-Tyr)₃ (PEG₈-(FY)3) or PEG₈-(Tyr)₆ (PEG₈-Y6) affects the structural/functional properties of the nanomaterial formed by the parental compound. Moreover, the effect of the PEG derivatization was evaluated through the characterization of the peptides without the PEG moiety (Tyr)₆ (Y6) and (Phe-Tyr)₃ ((FY)3). Both PEG₈-Y6 and PEG₈-(FY)3 can self-assemble in water at micromolar concentrations in β-sheet-rich nanostructures. However, WAXS diffraction patterns of these compounds present significant differences. PEG₈-(FY)3 shows a 2D WAXS oriented fiber diffraction profile characterized by the concomitant presence of a 4.7 Å meridional and a 12.5 Å equatorial reflection that are generally associated with cross-β structure. On the other hand, the pattern of PEG₈-Y6 is characterized by the presence of circles typically observed in the presence of PEG crystallization. Molecular modeling and dynamics provide an atomic structural model of the peptide spine of these compounds that is in good agreement with WAXS experimental data. Gelation phenomenon was only detected for PEG₈-(FY)3 above a concentration of 1.0 wt % as confirmed by storage (G′≈100 Pa) and loss (G′′≈28 Pa) moduli in rheological studies. The cell viability on CHO cells of this soft hydrogel was certified to be 90 % after 24 hours of incubation.