Unfolding of β-amyloid from MPP+ derivatives

DOI: 10.5176/2301-3761_CCECP16.24

Authors: Sandun Gajaweera, Rohan P. Perera and Samantha Weerasinghe

Abstract:

The major component of amyloid plaques are the β-amyloid peptides with residues from 1- 39 to 1 – 42 amino acids. The peptide with a length of 1 – 42 amino acids is observed to have the highest percentage in plaques. Amyloid toxicity is caused by an intermediate species in the path to aggregation called amyloid oligomers. The β-amyloid changes from its native helical state into an activated monomer which begins the path to aggregation. The unfolding of the β-amyloid monomer from its helical structure plays a key role in the aggregation mechanism. Using novel ligand molecules to unfold the β-amyloid protein can give insight into unfolding mechanism of the monomer. In this study N-methyl-4-phenylpyridinium (MPP+) derivatives are used as models to study the unfolding of the 1-42 β-amyloid protein. Out of the four derivatives used in this study, 4′-trifluromethyl-MPP+ showed an initiation of unfolding the β-amyloid protein. Furthermore 3′-hydroxy-MPP+ molecule had a tendency to trap the β-amyloid monomer in a helical state.

Keywords: Alzheimer’s disease; β-amyloid; Molecular docking; Molecular dynamics