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Inhibiting and Reversing Amyloid-β Peptide (1-40) Fibril Formation with Gramicidin S and Engineered Analogues
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
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2013 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 19, no 51, 17338-17348 p.Article in journal (Refereed) Published
Abstract [en]

In Alzheimer's disease, amyloid-β (Aβ) peptides aggregate into extracellular fibrillar deposits. Although these deposits may not be the prime cause of the neurodegeneration that characterizes this disease, inhibition or dissolution of amyloid fibril formation by Aβ peptides is likely to affect its development. ThT fluorescence measurements and AFM images showed that the natural antibiotic gramicidin S significantly inhibited Aβ amyloid formation in vitro and could dissolve amyloids that had formed in the absence of the antibiotic. In silico docking suggested that gramicidin S, a cyclic decapeptide that adopts a β-sheet conformation, binds to the Aβ peptide hairpin-stacked fibril through β-sheet interactions. This may explain why gramicidin S reduces fibril formation. Analogues of gramicidin S were also tested. An analogue with a potency that was four-times higher than that of the natural product was identified.

Place, publisher, year, edition, pages
2013. Vol. 19, no 51, 17338-17348 p.
Keyword [en]
Alzheimer’s disease, amyloid-beta peptides, antibiotics, fibrillization, structure–activity relationships
National Category
Biochemistry and Molecular Biology
URN: urn:nbn:se:su:diva-98629DOI: 10.1002/chem.201301535ISI: 000327889800015PubMedID: 24218178OAI: diva2:684684
Swedish Research Council

Funding agencies:

NOW top grant; Swedish Research Council; Xunta de Galicia Angeles Alvarino fellowship; European Social Fund 

Available from: 2014-01-08 Created: 2014-01-08 Last updated: 2014-01-20Bibliographically approved

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Wärmländer, Sebastian K T SGräslund, Astrid
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