title: 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.affiliation: Department of Chemical Engineering, University of Arkansas , 3202 Bell Engineering Center, Fayetteville, Arkansas 72701, United States.
authors.forename: J Phillip
authors.initials: JP
authors.lastname: Turner
authors.forename: Tammy
authors.initials: T
authors.lastname: Lutz-Rechtin
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Moore
authors.forename: Lauren
authors.initials: L
authors.lastname: Rogers
authors.forename: Omkar
authors.initials: O
authors.lastname: Bhave
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Moss
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Servoss
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D052160:Benzothiazoles; D001667:Binding, Competitive; D002942:Circular Dichroism; D005453:Fluorescence; D015151:Immunoblotting; D010446:Peptide Fragments / Q000737:chemistry*; D034444:Peptoids / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013844:Thiazoles / Q000737:chemistry; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D010446:Peptide Fragments; D034444:Peptoids; D013844:Thiazoles; C078592:amyloid beta-protein (1-40); C529399:amyloid beta-protein (16-20); C009462:thioflavin T