Gadolinium containing telechelic PEG‐polymers end‐capped by di‐phenylalanine motives as potential supramolecular MRI contrast agents

Abstract

Telechelic PEG-polymers end-capped by diphenylalanine (FF) motives and containing a DOTA-Gd complex, bound on a lysine side chain at the centre of peptide moiety, are studied for their assembling properties and for the relaxometric behavior. The observed variations in terms of relaxivity are correlated to the assembling properties of the aggregates by using several techniques: fluorescence, Circular Dichroism (CD) and Fourier Transform Infrared (FTIR) for aggregation tendency and secondary structure determination; Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM) for morphological definition. Self-aggregation in water solution of the peptide conjugates, due to interaction of the phenylalanine frameworks, starts at concentration around 1 mg/ml with a first evidence of the coexistence of fibrillary networks and hydrogels at 10 mg/ml. Definitive presence of well-structured fibrillary networks, dominated by an antiparallel β-sheet arrangement, occurs at 50 mg/ml. At the latter concentration relaxivity values measured at 20 MHz and 298 K, are around 11 mM s , in line with a possible use of the these aggregates as MRI contrast agents. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

Fluorescence Phenomena in Amyloid and Amyloidogenic Bionanostructures

“…An increase in emission is referred to as a consequence of dye binding to hydrophobic tasks. According to these considerations, ANS was evaluated as a useful fluorophore for kinetic studies, the determination of critical aggregation concentration and the equilibrium study of amyloids [57][58][59] It was also used to assess the influence of various external factors (i.e., concentration, pH, presence of molecular inhibitors) on the assembly. ANS and its analog bis-ANS ( Figure 3, ANS) were found to be capable of efficiently detecting the kinetics of Aβ amyloid aggregation, while not affecting the morphologies, as demonstrated by TEM.…”

Photoluminescent Peptide‐Based Nanostructures as FRET Donor for Fluorophore Dye

“…However, the low water solubility of these peptide NSs has partially limited their application in nanomedicine. Very recently, we described the first examples of NSs based on PEGylated (PEG=polyethylene glycol) cationic poly‐phenylalanines or their analogues (di‐naphthylalanine) for bio‐imaging applications. These peptide derivatives contain an aromatic region to allow the self‐assembly of the NS, a gadolinium (Gd) complex for applications as in vivo contrast agent in magnetic resonance imaging (MRI), and a PEG spacer at different length between the Gd‐complex and the peptide moiety.…”

“…[10] However, the low water solubility of these peptideN Ss has partially limited their application in nanomedicine. Very recently,w ed escribed the first examples of NSs based on PEGylated (PEG = polyethylene glycol)c ationic poly-phenylalanines [5b, 8,11] or their analogues (di-naphthylalanine) [12] for bio-imaging applications.T hese peptided erivatives contain an aromatic region to allow the self-assembly of the NS, ag adolinium (Gd) complex for applications as in vivo contrast agent in magnetic resonance imaging (MRI), and aP EG spacera tdifferent length between the Gd-complex and the peptidem oiety.T hese peptidesc ouldb ep otentially proposed for applicationi nM RI owing tot heir high uptake and moderately low toxicityo ns electedc ell lines. [8] In more recent years, ag reat interest has been generated around peptide-based NSs with interesting photoluminescent (PL) properties.…”

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

“…4A). Recently, Diaferia et al 41,42 developed several examples of aromatic peptide conjugates for use as MRI-CAs. The idea of using aromatic short peptides (containing two or three residues) as building blocks to prompt ber formation originated from the large amount of published literature on the ultra-short homodipeptide Phe-Phe (FF or F2), a dipeptide identied for the rst time by Gazit in 2003 as an aggregating core motif for the Ab-amyloid peptides (Ab1-40 and Ab1-42).…”