Hierarchical Analysis of Self‐Assembled PEGylated Hexaphenylalanine Photoluminescent Nanostructures

Abstract

Despite the growing literature about diphenylalanine-based peptide materials, it still remains a challenge to delineate the theoretical insight into peptide nanostructure formation and the structural features that could permit materials with enhanced properties to be engineered. Herein, we report the synthesis of a novel peptide building block composed of six phenylalanine residues and eight PEG units, PEG -F6. This aromatic peptide self-assembles in water in stable and well-ordered nanostructures with optoelectronic properties. A variety of techniques, such as fluorescence, FTIR, CD, DLS, SEM, SAXS, and WAXS allowed us to correlate the photoluminescence properties of the self-assembled nanostructures with the structural organization of the peptide building block at the micro- and nanoscale. Finally, a model of hexaphenylalanine in aqueous solution by molecular dynamics simulations is presented to suggest structural and energetic factors controlling the formation of nanostructures.

Photoluminescent Peptide‐Based Nanostructures as FRET Donor for Fluorophore Dye

“…Owing to the close relationship between the optoelectronic properties and the structural motif in these systems, PL is currently used as a promising probe to detect the formation of amyloid fibrils. We demonstrated that empty PEG 8 ‐F6‐based NSs, at a concentration of 10 mg mL −1 , are able to emit at 460 nm (Figure S3 in the Supporting Information) . At this very high concentration it was possible to detect a broad peak between 370 and 410 nm in the UV/Vis spectrum (Figure S4 in the Supporting Information), partially affected by the tail of the main absorbance peak centered at 257 nm, which is typical for the phenyl ring.…”

“…Recently, several authors reported a surprising PL phenomenon for fibrillary networks such as amyloid fibrils and for peptide‐based NSs, both of them characterized by a high content of cross‐β structures . These systems show a fluorescence emission peak at 460 nm when excited at 370 or at 410 nm.…”

“…Some hypotheses on the origin of this PL, such as electron delocalization through hydrogen bonds in the β‐sheet‐rich structure or proton transfer, have been proposed until now. We recently reported on the synthesis and structural characterization of a novel PEGylated hexaphenylalanine peptide, PEG 8 ‐F6 (Figure a), made of aromatic and hydrophilic moieties, which forms NSs with remarkable PL properties . The structural characterization of PEG 8 ‐F6 in solution highlighted its strong propensity to self‐assemble in stable and well‐organized NSs with a hydrodynamic diameter of approximately 60 nm and an antiparallel β‐sheet arrangement.…”

“…Wide‐angle X‐ray scattering (WAXS) characterization on dried fibers also revealed a typical cross‐β diffraction pattern observed for amyloid‐like fibers with meridional and equatorial peaks at 4.8 and 12.5 Å, respectively. PEG 8 ‐F6 NSs showed a blue PL between 420 and 460 nm when excited at wavelengths of 370 or 410 nm . Here, we explored the possibility to transfer by foster resonance electron transfer (FRET) phenomenon the fluorescence of a cross‐β material (donor) such as PEG 8 ‐F6‐based NSs into an encapsulated fluorescent dye such as 4‐chloro‐7‐nitrobenzofurazan (NBD, Figure b).…”

Peptide Nanophotonics: From Optical Waveguiding to Precise Medicine and Multifunctional Biochips

“…In contrast to well‐known biomaterials' counterparts applied in implantable photonics, for instance, silk fibers, polymers, hydrogels, and more, these peptide‐based nanostructures have significantly higher refractive index ≈1.6 providing strong optical confinement of peptide optical waveguides . Another key functional optical effect is a new phenomenon of intrinsic tunable visible fluorescence (FL) recently revealed in different bioinspired peptide nanostructures …”