Document Type

Article

Publication Date

2018

Keywords

Amyloid, inhibitor, Thioflavin T assay, Hemolysis, TEM, Human insulin

Digital Object Identifier (DOI)

https://doi.org/10.3389/fchem.2018.00311

Abstract

Inhibition of fibrillation process and disaggregation of mature fibrils using small peptide are the promising remedial strategies to combat neurodegenerative diseases. However, designing peptide-based drugs to target β-sheet-rich amyloid has been a major challenge. The current work describes, for the first time, the amyloid inhibitory potential of the two short peptides (selected on the basis of predisposition of their amino acid residues toward β-sheet formation) using combination of biophysical, imaging methods, and docking approaches. Results showed that peptides employed different mechanisms to inhibit the amyloid fibrillation. Furthermore, they were also effective in blocking the amyloid fibrillation pathway. In contrary to the insulin fibrillar mesh, significantly less fibrillar species appeared in the presence of peptides, as confirmed by transmission electron microscopy. Circular dichroism analysis indicated that although peptides did not stabilize the native state of insulin, they inhibited amyloid aggregation by reducing the formation of β-sheet rich structures. Hemolytic assay revealed the non-hemolytic nature of the species formed when insulin was co-incubated with the peptides. Therefore, despite the inherent potential to form β-sheet structure, these peptides inhibited the amyloid formation and potentially can be used as therapeutics for the treatment of amyloid-related diseases

Rights Information

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Was this content written or created while at USF?

Yes

Citation / Publisher Attribution

Frontiers in Chemistry, v. 6, art. 311

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