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Aromatic‐interaction‐mediated inhibition of β‐amyloid assembly structures and cytotoxicity
Author(s) -
Xie Hanyi,
Peng Jiaxi,
Liu Changliang,
Fang Xiaocui,
Duan Hongyang,
Zou Yimin,
Yang Yanlian,
Wang Chen
Publication year - 2017
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.3011
Subject(s) - chemistry , thioflavin , aromatic amino acids , peptide , cytotoxicity , circular dichroism , amino acid , amyloid (mycology) , tryptophan , tyrosine , biochemistry , hydrogen bond , fibril , docking (animal) , stereochemistry , in vitro , alzheimer's disease , organic chemistry , molecule , medicine , inorganic chemistry , nursing , disease , pathology
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. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.