The incidence of amyloid diseases, including Alzheimer’s and Parkinsons disease, in the global population has increased significantly in the past few years. The hallmark of such diseases, is the formation of misfolded amyloid plaques that aggregate extracellularly in the brain and are cytotoxic. There are currently few approved treatment options that specifically address the pathology of these amyloid-based diseases, though there have been studies that employ designed peptides, metal nanoparticles, polyphenols, and certain ionic liquids for amyloid defibrillation. In this work, we conducted computational studies using three newly designed plant based polyphenol-amino acid conjugates that may be potentially be applicable in mitigating beta-amyloid and alpha-synuclein aggregation. The self-assembly of the conjugates was simulated using Gromacs in a solvent containing a salt concentration similar to plasma to mimic the initial metabolism of the drug in the circulatory system. Autodock Vina, Biotec’s Protein-Ligand Interaction Profiler, and Metapocket were used to study the interactions of the drugs with β-amyloid(1-40). SwissADME was used to examine the pharmacokinetic and cytotoxic properties of the conjugates. We found that the designed conjugates had better affinities for β-amyloid(1-40) in comparison to the neat polyphenol and amino acids. The conjugates also had favorable pharmacokinetic properties and low cytotoxicity. Such polyphenol-amino acid drug conjugates may have potential applications in reducing protein misfolding that causes beta-amyloid plaques and alpha-synuclein aggregates and thereby may have potential applications in alleviating neurodegenerative diseases.

Computational analysis of amino acid-polyphenol conjugates as potential therapeutics for amyloid-based diseases

ACS Spring Meeting 2021

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