title: Effect of replacing phenylalanine residues by para-substituted phenylalanines on the aggregation behavior of aβ16-22.
abstract: The peptide sequence KLVFFAE that spans the region 16-22 in the amyloid peptide Aβ1-40 has the ability to form fibrils or nanotubes in aqueous medium, depending on the conditions of dissolution. Interaction between the phenylalanine residues is presumed to play an important role in the self-assembly of Aβ16-22. We have investigated the importance of these aromatic residues by substituting them with p-chloro-, p-fluoro- and p-methylphenylalanine. Nanostructures different from the parent peptide were obtained with the substituted analogs, both in methanol as well as aqueous conditions (pH 2 and pH 7). Concentration-dependent effects observed in methanol, suggest that intermediate states occur during fibrillation. A balance between the crucial parameters such as charge, hydrophobicity and steric constraints implicated in self assembly, appear to modulate the nanostructure formation.
authors.affiliation: Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, INDIA.
authors.forename: Chandrasekaran
authors.initials: C
authors.lastname: Sivakamasundari
authors.forename: Sasi
authors.initials: S
authors.lastname: Nandakumar
authors.forename: Ramakrishnan
authors.initials: R
authors.lastname: Nagaraj
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D000432:Methanol / Q000737:chemistry; D049329:Nanostructures / Q000737:chemistry / Q000648:ultrastructure; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C417223:amyloid beta-protein (16-22); D014867:Water; D010649:Phenylalanine; D000432:Methanol