Fibril aggregation inhibitory activity of the β-sheet breaker peptides: a molecular docking approach

✍ Scribed by Maria Giovanna Chini; Mario Scrima; Anna Maria D'Ursi; Giuseppe Bifulco

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 324 KB
• Volume: 15
• Category: Article
• ISSN: 1075-2617
• DOI: 10.1002/psc.1095

✦ Synopsis

Abstract

In the present study, we used a molecular docking as a rapid, interactive method to study the inhibition of fibrillogenesis process by β‐sheet breaker peptide (BSB) (Ac‐L^1^‐V^2^‐(NMet)F^3^‐F^4^‐A^5^‐NH~2~). Our aim was to find the complex (Aβ:BSB) that blocks the aggregation of the fibrils, and to identify the binding sequences for the small peptides on Aβ~1–42~. An NMR structure solved by Lührs et al. in 2005 was used to study the interaction of BSB with the amyloid aggregated forms. From our preliminary step‐by‐step docking studies, the L(17)‐D(23) sequence seems to be one of the most common active sites of Aβ~1–42~, and critical in amyloid fibril formation. We note that a single molecule of BSB does not influence the interaction between the two fibrils, while a little excess of BSB (two molecules) with respect to the amyloid does not completely block but undoubtedly obstructs the aggregation process. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.