Fibrillogenesis in ADan peptides is inhibited by biphenyl ethers |
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Authors: | Surolia Ira Chhibber Manmohan Sarkar Debi Prasad Sinha Sharmistha |
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Institution: | a Department of Biochemistry, South Campus, University of Delhi, New Delhi 110021, India b Molecular Biophysics Unit, Indian Institute of Science, Lab, 204, CV Raman Avenue, Bangalore 560012, India |
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Abstract: | In this study, biphenyl ethers of diverse functionality were used to assess their effect on fibrillogenesis of both the oxidized and reduced ADan peptides, in vitro. It was noted that these compounds not only stalled fibrillogenesis but were also able to disrupt pre-formed fibers. The EC50 values for the inhibition of this process lie in the nanomolar range for 50 μM of peptide concentration, indicating the high potency of these compounds as inhibitors. It was found that these compounds impart to the peptides, an α-helical conformation which does not allow them to aggregate and form fibrils. These studies also point out that the transition of peptides through α-helical conformation may be a prelude to the onset of fibrillogenesis for oxADan peptides. |
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Keywords: | Danish dementia Amyloid Inhibition Fibers Biphenyl ethers |
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