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J Pept Sci. 2017 Sep;23(9):679-684. doi: 10.1002/psc.3011. Epub 2017 May 23.

Aromatic-interaction-mediated inhibition of β-amyloid assembly structures and cytotoxicity.

Author information

1
CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Key Laboratory of Standardization and Measurement for Nanotechnology of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, CAS Center for Excellence in Brain Science, National Center for Nanoscience and Technology, Beijing, 100190, PR China.
2
Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, PR China.

Abstract

Abnormal aggregation of β-amyloid (Aβ) peptide plays an important role in the onset and progress of Alzheimer's disease (AD); hence, targeting Aβ aggregation is considered as an effective therapeutic strategy. Here, we studied the aromatic-interaction-mediated inhibitory effect of oligomeric polypeptides (K8Y8, K4Y8, K8W8) on Aβ42 fibrillization process. The polypeptides containing lysine as well as representative aromatic amino acids of tryptophan or tyrosine were found to greatly suppress the aggregation as evaluated by thioflavin T assay. Circular dichroism spectra showed that the β-sheet formation of Aβ42 peptides decreased with the polypeptide additives. Molecular docking studies revealed that the oligomeric polypeptides could preferentially bind to Aβ42 through π-π stacking between aromatic amino acids and Phe19, together with hydrogen bonding. The cell viability assay confirmed that the toxicity of Aβ42 to SH-SY5Y cells was markedly reduced in the presence of polypeptides. This study could be beneficial for developing peptide-based inhibitory agents for amyloidoses.

KEYWORDS:

abeta; aggregation; aromatic-interaction; inhibition

PMID:
28543807
DOI:
10.1002/psc.3011
[Indexed for MEDLINE]

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