Rationally designed peptoids modulate aggregation of amyloid-beta 40.

Abstract

Alzheimer's disease (AD) is the most common form of dementia and the sixth leading cause of death in the United States. Plaques composed of aggregated amyloid-beta protein (Aβ) accumulate between the neural cells in the brain and are associated with dementia and cellular death. Many strategies have been investigated to prevent Aβ self-assembly into disease-associated β-sheet amyloid aggregates; however, a promising therapeutic has not yet been identified. In this study, a peptoid-based mimic of the peptide KLVFF (residues 16-20 of Aβ) was tested for its ability to modulate Aβ aggregation. Peptoid JPT1 includes chiral, aromatic side chains to induce formation of a stable helical secondary structure that allows for greater interaction between the aromatic side chains and the cross β-sheet of Aβ. JPT1 was found to modulate Aβ40 aggregation, specifically decreasing lag time to β-sheet aggregate formation as well as the total number of fibrillar, β-sheet structured aggregates formed. These results suggest that peptoids may be able to limit the formation of Aβ aggregates that are associated with AD.

• Authors: J Phillip Turner, Tammy Lutz-Rechtin, Kelly A Moore, Lauren Rogers, Omkar Bhave, Melissa A Moss, Shannon L Servoss
• Journal: ACS chemical neuroscience (ACS Chem Neurosci) Vol. 5 Issue 7 Pg. 552-8 (Jul 16 2014) ISSN: 1948-7193 [Electronic] United States
• PMID: 24689364 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Amyloid beta-Peptides
• Benzothiazoles
• Peptide Fragments
• Peptoids
• Thiazoles
• amyloid beta-protein (1-40)
• amyloid beta-protein (16-20)
• thioflavin T

Topics

• Amyloid beta-Peptides (chemistry)
• Benzothiazoles
• Binding, Competitive
• Circular Dichroism
• Fluorescence
• Immunoblotting
• Peptide Fragments (chemistry)
• Peptoids (chemistry)
• Protein Structure, Secondary
• Thiazoles (chemistry)
• Time Factors