当前位置： SCI文献检索 > INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES期刊下所有文献 > Inhibition of amyloid fibrillation of γD-crystallin model peptide by the cochineal Carmine.

Inhibition of amyloid fibrillation of γD-crystallin model peptide by the cochineal Carmine.

Abstract：

:γD-crystallin is among the most abundant γ-crystallins in the human eye lens which are essential for preserving its transparency. Aging, and environmental changes, cause crystallins to lose their native soluble structure and aggregate, resulting in the formation of cataract. Current treatment of cataract is surgical removal which is costly. Pharmaceutical therapeutics of cataract is an unmet need. We report a screen for small molecules capable of inhibiting aggregation of human γD-crystallin. Using a highly amyloidogenic hexapeptide model 41GCWMLY46 derived from the full-length protein, we screened a library of 68 anthraquinone molecules using ThT fluorescence assay. A leading hit, the cochineal Carmine, effectively reduced aggregation of the model GDC6 peptide in dose dependent manner. Similar effect was observed toward aggregation of the full-length γD-crystallin. Transmission electron microscopy, intrinsic Tryptophan fluorescence and ANS fluorescence assays corroborated these results. Insights obtained from molecular docking suggested that Carmine interaction with monomeric GDC6 involved hydrogen bonding with Ace group, Cys, Met residues and hydrophobic contact with Trp residue. Carmine was non-toxic toward retinal cells in culture. It also reduced ex vivo the turbidity of human extracted cataract material. Collectively, our results indicate that Carmine could be used for developing new therapeutics to treat cataract.

journal_name

Int J Biol Macromol

journal_title

International journal of biological macromolecules

authors

Abu-Hussien M,Viswanathan GK,Borisover L,Mimouni M,Engel H,Zayit-Soudry S,Gazit E,Segal D

doi

10.1016/j.ijbiomac.2020.12.106

subject

Has Abstract

pub_date

2021-02-01 00:00:00

pages

342-351

eissn

0141-8130

issn

1879-0003

pii

S0141-8130(20)35263-6

journal_volume

169

pub_type

杂志文章

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