Poly(4-styrenesulfonate) as an Inhibitor of A尾40 Amyloid Fibril Formation

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• 作者：Bimlesh Ojha ; Haiyang Liu ; Samrat Dutta ; Praveen P. N. Rao ; Ewa P. Wojcikiewicz ; Deguo Du
• 刊名：Journal of Physical Chemistry B
• 出版年：2013
• 出版时间：November 14, 2013
• 年：2013
• 卷：117
• 期：45
• 页码：13975-13984
• 全文大小：481K
• 年卷期：v.117,no.45(November 14, 2013)
• ISSN：1520-5207

文摘

The formation of amyloid, a cross-尾-sheet fibrillar aggregate of proteins, is associated with a variety of neurodegenerative diseases. Amyloidogenic proteins such as 尾-amyloid (A尾) are known to exist with a large amount of polyelectrolyte macromolecules in vivo. The exact nature of A尾鈥損olyelectrolyte interactions and their roles in A尾-aggregation are largely unknown. In this regard, we report the inhibiting effect of an anionic polyelectrolyte poly(4-styrenesulfonate) (PSS) on the aggregation of A尾40 peptide. The results demonstrate the strong inhibition potential of PSS on the aggregation of A尾40 and imply the dominant role of hydrophobicity of the polyelectrolyte in reducing the propensity of A尾40 amyloid formation. Additional studies with poly(vinyl sulfate) (PVS) and p-toluenesulfonate (PTS), which share similar charge density with PSS except the former lacking the nonpolar aromatic side chain and the latter the aliphatic hydrocarbon backbone, reveal that the presence of both aliphatic backbone and aromatic side chain group in PSS is essential for its A尾-aggregation inhibition activity. The interactions involved in the A尾40鈥揚SS complex were further investigated using molecular dynamics (MD) simulation. Our results provide new insights into the structural interplay between polyelectrolytes and A尾 peptide, facilitating the ultimate understanding of amyloid formation in Alzheimer鈥檚 disease. The results should assist in developing novel polyelectrolytes as potential chemical tools to study amyloid aggregation.