Amyloidogenic Properties of Short α-l-Glutamic Acid Oligomers

Abstract

Poly-L-glutamic acid (PLGA) forms amyloid-like β2-fibrils with the main spectral component of vibrational amide I' band unusually shifted below 1600 cm(-1). This distinct infrared feature has been attributed to the presence of bifurcated hydrogen bonds coupling C═O and N-D (N-H) groups of the main chains to glutamate side chains. Here, we investigate how decreasing the chain length of PLGA affects its capacity to form β2-fibrils. A series of acidified aqueous solutions of synthetic (l-Glu)n peptides (n ≈ 200, 10, 6, 5, 4, and 3) were incubated at high temperature. We observed that n = 4 is the critical chain length for which formation of aggregates with the β2-like infrared features is still observed under such conditions. Interestingly, according to atomic force microscopy (AFM), the self-assembly of (L-Glu)n chains varying vastly in length produces fibrils with rather uniform diameters of approximately 4-6 nm. Kinetic experiments on (L-Glu)5 and (L-Glu)200 peptides indicate that the fibrillation is significantly accelerated not only in the presence of homologous seeds but also upon cross-seeding, suggesting thereby a common self-assembly theme for (L-Glu)n chains of various lengths. Our results are discussed in the context of mechanisms of amyloidogenic fibrillation of homopolypeptides.

Amyloidogenic cross-seeding of Tau protein: Transient emergence of structural variants of fibrils

“…Our interests have been focused on the persistence of structural phenotypes of mother amyloid seeds from these amyloidogenic substrates upon multiple rounds of cross-seeding to FL Tau monomers in the presence of poly-Glu as a polyanionic inducer of aggregation. It is important to stress that while poly-Glu may form, under certain conditions, amyloid-like fibrils (which has been shown previously [ 32 – 34 ]) that requires lowering pH so that Glu side-chains are reprotonated and neutral. However, at pH 6 used in this study poly-Glu itself is unable to adopt the amyloid-like state [ 33 ].…”

Interactions of rationally designed small peptide dendrons functionalized with valine or sinapic acid with α‐helix and β‐sheet structures of poly‐l‐lysine and poly‐l‐glutamic acid

“…; for PLGA >50 000 a.u.) Literature data regarding the generation of random, α‐helix, and most of all β‐sheet structures from such samples report different conditions and therefore, the necessary first step was to establish pH, temperature and time ranges for the formation of a particular secondary structure in solution. According to our experiments, at pH 12, the water solution of PLL revealed a well resolved α‐helix conformation, whereas further heating to 52 °C for 15 minutes induced an α‐helix to β‐sheet transformation (Figure ).…”

“…Several studies have shown that the aggregation propensity of homo‐polypeptides ( e.g ., polyglutamine, Aib homo‐polypeptides, and PLGA) depends on the polypeptide. Moreover, polydispersity of the sample in terms of chain length enhances transformation between unstructured monomeric and structured aggregated forms . Here we used polydispersed PLL or PLGA homo‐polypeptides for the preparation of proteinaceous secondary structures.…”

Interactions of Glycopolymers with Assemblies of Peptide Amphiphiles via Dynamic Covalent Bonding

“…Both the hydrophobic interaction of the 18-carbon alkyl chain, and the formation of β-sheet peptide secondary structure are the driving forces for the assembly. In Fourier transform infrared (FT-IR) spectrum (Figure S5), the peak at 1632 cm –1 (C = O, amide I) indicates the formation of β-sheet, ,, while a shoulder peak at about 1641 cm –1 may result from the transition from β-sheet to helix on the edge of PAA . A red shift of −COOH peak from 1720 to 1697 cm –1 showed the effect of hydrogen bonding .…”