Amyloidogenic Properties of Short α-L-Glutamic Acid Oligomers.

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 signif...