Self-association of different proteins and peptides are often found to be responsible for the formation of amyloid fibrils which lead to neuropathogenesis. The senile plaques that make up the fibrils mainly contain the 42–residue long amyloid beta (Aβ) peptide along with its shorter fragments. Of these fragments, the Aβ peptide 25–35 fragment (Aβ25–35) acts as a model fragment because of its ability to fibrillate rapidly. The inhibition of the fibrillation process in these peptides has been a topic of study for less than a decade and novel compounds and ligands are sought after to check their efficacy in the inhibition of fibrialltion. Graphene oxide (GO), a two dimesional nanomaterial is found to block the Aβ25–35 peptide fibrillation effectively. The self-association process of Aβ25–35 peptide and its inhibition by GO has been performed in vitro at pH 7.4 and physiological temperature (37 °C). Several biophysical methods like Thioflavin T (ThT) fluorescence, circular dichroism spectroscopy, matrix assisted laser desorption/ionization mass spectrometry, dynamic light scattering experiments, Fourier transform infrared spectroscopy have been employed to study the inhibition process. The quantification of the soluble protein fraction is obtained by UV-visible spectroscopy based bicinchoninic acid assay. Microscopic techniques are also used to monitor the morphological evolution of the peptide in presence and absence of GO. ThT kinetics showed that GO results in elongation of the lag phase of the Aβ25–35 peptide fibrillation process. A comparison between the inhibitory activity of GO on Aβ25–35 peptide fibrillation and previously reported Aβ33–42 peptide fibrillation showed that lower hydrophobicity (obtained from hydropathy scores - that is a measure of the extent of hydrophobicity) of the Aβ25–35 peptide over the Aβ33–42 peptide facilitates the inhibition process. GO is found to inhibit Aβ25–35 peptide even at very low concetration of GO as compared to Aβ33–42 peptide. It is speculated that surface adsorption of the Aβ25–35 peptide monomers on the GO surface by various non-bonding forces, predominantly through the electrostatic interactions between protonated the amino group of Lys–28 and carboxylate moiety of GO at physiological pH results in efficient inhibition of the fibrillation process.

Prevention of fibrillation of the amyloid-β (25-35) peptide by graphene oxide

253rd National Meeting (2017)

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