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

Abstract

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 PEG -(Phe) (PEG -F6) with tyrosines to generate PEG -(Phe-Tyr) (PEG -(FY)3) or PEG -(Tyr) (PEG -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) (Y6) and (Phe-Tyr) ((FY)3). Both PEG -Y6 and PEG -(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. PEG -(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 PEG -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 PEG -(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.

Systematic overview of soft materials as a novel frontier for MRI contrast agents

“…A further increase in the concentration (above 20 mg mL À1 ) brought about the formation of a hydrogel such as those of other PEGylated analogues. 46,47 In line with the other systems previously described, these gels exhibited a r 1p value of 12.3 mM À1 s À1 at 20 MHz and a satisfactory capability to encapsulate anticancer drugs, such as doxorubicin. According to this strategy, in 2016 Lee and coworkers proposed a similar multifunctional theranostic nanoplatform, loaded with Gd-complexes and doxorubicin, for application in personalized medicine.…”

Molecular Simulations of PEGylated Biomolecules, Liposomes, and Nanoparticles for Drug Delivery Applications

“…Khameneh et al simulated PEGylated human growth hormone with its receptor and performed the docking analysis, showing the random-coil formation of PEG and the reduced binding affinity between human growth hormone and its receptor in the presence of PEG [54]. The Accardo group simulated PEGylated hexa-phenylalanine [55,56], tetra-tryptophan [57], and tyrosine-containing aromatic peptides [58], showing the effect of PEGylation on the conformation and stability of assembled structures.…”

Fluorescence Phenomena in Amyloid and Amyloidogenic Bionanostructures

“…Partially folded intermediate aggregative states, having solvent-exposed hydrophobic clusters, can be detected using aggregation-induced emission probes, such as ANS (Figure 3, ANS) dye [55]. ANS has low fluorescence quantum yield in aqueous environments, whereas its emission is dramatically increased in non-polar ones, like self-assembling peptide spines [56]. An increase in emission is referred to as a consequence of dye binding to hydrophobic tasks.…”