Nanostructures Formed by Custom-Made Peptides Based on Amyloid Peptide Sequences and Their Inhibition by 2-Hydroxynaphthoquinone.

Radhika Mannem,Lakshmaiah Sreerama,Mohammed Yousuf

doi:10.3389/fchem.2020.00684

Abstract

Extensive research on amyloid fibril formations shows that certain core sequences within Aβ peptide play an important role in their formation. It is impossible to track these events in vivo. Many proteins and peptides with such core sequences form amyloid fibrils and such Aβ sheet mimics have become excellent tools to study amyloid fibril formation and develop therapeutic strategies. A group of peptides based on amyloid peptide sequences obtained from PDB searches, where glycine residues are substituted with alanine and isoleucine, are tested for aggregation by SEM and ThT binding assay. SEM of different peptide sequences showed morphologically different structures such as nanorods, crystalline needles and nanofibrils. The peptides were co-incubated with HNQ (a quinone) to study its effect on the process of aggregation and/or fibrillation. In conclusion, this group of peptides seem to be Aβ sheet mimics and can be very useful in understanding the different morphologies of amyloid fibrils arising from different peptide sequences and the effective strategies to inhibit or anneal them.

Highlights

Amyloid formation has been proven to be the underlying trigger for a number of protein deposition diseases like Alzheimer’s, Parkinson’s, diabetes, β2m-amyloidosis, carpel tunnel syndrome, destructive arthropathy, transthyretin amyloidosis, transmissible spongiform encephalopathy, hemodialysis related amyloidosis etc. (Bucciantini et al, 2002; Bu et al, 2007; Siddiqi et al, 2018)
This study focuses on the structures formed by a variety of peptide sequences and evaluate the effect of quinone (HNQ) on these structures as examined by Scanning Electron Microscopy (SEM), thioflavin T (ThT) binding assay, and FT-IR spectroscopy
In a comparison between the nanostructures formed by KI4K and KKI4, it was concluded that the electrostatic repulsive forces from 2 lysine residues at the N-terminus weaken the hydrophobic adhesion between the isoleucine residues

Summary

Introduction

Amyloid formation has been proven to be the underlying trigger for a number of protein deposition diseases like Alzheimer’s, Parkinson’s, diabetes, β2m-amyloidosis, carpel tunnel syndrome, destructive arthropathy, transthyretin amyloidosis, transmissible spongiform encephalopathy, hemodialysis related amyloidosis etc. (Bucciantini et al, 2002; Bu et al, 2007; Siddiqi et al, 2018). Amyloid formation has been proven to be the underlying trigger for a number of protein deposition diseases like Alzheimer’s, Parkinson’s, diabetes, β2m-amyloidosis, carpel tunnel syndrome, destructive arthropathy, transthyretin amyloidosis, transmissible spongiform encephalopathy, hemodialysis related amyloidosis etc. The self-assembly of amyloid proteins into fibrils has been found to be the basis for the pathogenic process in all these diseases (Bucciantini et al, 2002; Cuvalevski et al, 2012). Some proteins are found to misfold into amyloid fibrils which seems to be the primary cause in many diseases mentioned above. Much remains to be elucidated regarding the molecular mechanisms involved in the amyloid aggregation, the different entities formed down the cascade and the significance of peptide sequences in the formation of these entities (Tjernberg et al, 1999; Ivanova et al, 2006)

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Conclusion