title: Inhibition of beta-amyloid fibrillization by directed evolution of a beta-sheet presenting miniature protein.
abstract: We describe the directed evolution of a miniature beta-sheet protein for targeting beta-amyloid oligomers implicated in Alzheimer's disease. Circular dichroism spectroscopy, thermal denaturation experiments, and immunoglobulin binding assays established that our beta-amyloid-targeted miniature protein, TJ10, presents a well-folded thermostable beta-sheet. TJ10 was found to prevent beta-amyloid fibrillization at stoichiometric concentrations and was also an effective inhibitor at substoichiometric concentrations. Thus our results provide a new and potent beta-sheet chemical template for effectively targeting beta-amyloid while also demonstrating a general strategy for targeting proteins implicated in other amyloidogenic diseases.
authors.affiliation: Department of Chemistry, University of Arizona, Tucson, Arizona 85721, USA.
authors.forename: Thaddeus J
authors.initials: TJ
authors.lastname: Smith
authors.forename: Cliff I
authors.initials: CI
authors.lastname: Stains
authors.forename: Scott C
authors.initials: SC
authors.lastname: Meyer
authors.forename: Indraneel
authors.initials: I
authors.lastname: Ghosh
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry; D002942:Circular Dichroism; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data
chemical_list: D016229:Amyloid beta-Peptides