Amyloid-beta (Aβ) is a macromolecular structure of great interest since its misfolding and aggregation along with changes in the secondary structure has been correlated with its toxicity in various neurodegenerative diseases. Small drug-like molecules can modulate secondary structures of amyloids and, therefore, can be used for active and passive therapies for amyloid-related diseases. In this study, we investigated the interactions of epigallocatechin-3-gallate (EGCG), found in green tea, with amyloid-β polypeptides using a combination of in vitro immuno-infrared sensor, docking studies, MD simulation, and ab initio calculations. We find that the interactions are dominated by only a few residues of the fibril, ranging from hydrophobic π-π interaction with aromatic rings of the side chains to hydrophilic interactions with the backbones atoms of Aβ. We confirmed the robustness of the docking sites using extended MD simulations. Our MD simulation revealed an additional highly favored interaction site, which could not be obtained from docking to a static structure. The immuno-infrared sensor demonstrates that EGCG induces Aβ fibril degradation (also inhibition of Aβ fibril/oligomer formation) and, thus, recovers the amide-I band of monomeric Aβ red-shifted by 26 cm-1 compared to the amide-I band of the fibrillar form. We rationalize this shift by computing the IR spectra of model structures of Aβ42 and propose that the transformation is induced by interruption of the inter-chain hydrogen bonds in amyloid fibrils by EGCG molecules.

Effect of (-)-epigallocatechin-3-gallate on the Aβ secondary structure

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.