title: Oligo(p-phenylene ethynylene) Electrolytes: A Novel Molecular Scaffold for Optical Tracking of Amyloids.
abstract: Finding new optical probes to detect and track amyloid protein aggregates is key to understanding and defeating the myriad of neurodegenerative and other diseases associated with these misfolded proteins. Herein we report that a series of fluorescent, soluble oligo(p-phenylene ethynylene)s (OPEs) are able to detect amyloids in vitro by massive binding-activated superluminescence, with low micromolar affinity and high selectivity for the amyloid conformer. The OPEs track the kinetics of amyloid fibril formation from native hen egg white lysozyme (HEWL) similarly to thioflavin T (ThT), and the dependence of binding affinity on OPE length supports the theory of a linear binding groove. We hypothesize, based on spectral properties, induced circular dichroism, and previous work in analogous systems, that the fluorescence turn-on mechanism is a combination of the reduction of static solvent-mediated quenching at the ethyl ester end groups of the phenylene ethynylene fluorophore and the formation of chiral J-type aggregates templated on the amyloid fibril surface.
authors.affiliation: The Nanoscience and Microsystems Engineering Program, ‡Department of Chemical and Biological Engineering, and §The Center for Biomedical Engineering, University of New Mexico , Albuquerque, New Mexico 87131, United States.
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Donabedian
authors.affiliation: The Nanoscience and Microsystems Engineering Program, ‡Department of Chemical and Biological Engineering, and §The Center for Biomedical Engineering, University of New Mexico , Albuquerque, New Mexico 87131, United States.
authors.forename: Thao K
authors.initials: TK
authors.lastname: Pham
authors.affiliation: The Nanoscience and Microsystems Engineering Program, ‡Department of Chemical and Biological Engineering, and §The Center for Biomedical Engineering, University of New Mexico , Albuquerque, New Mexico 87131, United States.
authors.forename: David G
authors.initials: DG
authors.lastname: Whitten
authors.affiliation: The Nanoscience and Microsystems Engineering Program, ‡Department of Chemical and Biological Engineering, and §The Center for Biomedical Engineering, University of New Mexico , Albuquerque, New Mexico 87131, United States.
authors.forename: Eva Y
authors.initials: EY
authors.lastname: Chi
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D052160:Benzothiazoles; D002942:Circular Dichroism; D004573:Electrolytes / Q000138:chemical synthesis / Q000737:chemistry; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry; D007700:Kinetics; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D009113:Muramidase / Q000737:chemistry / Q000378:metabolism; D061848:Optical Imaging / Q000295:instrumentation / Q000379:methods*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry; D013053:Spectrophotometry; D013844:Thiazoles / Q000737:chemistry / Q000378:metabolism
chemical_list: D000682:Amyloid; D052160:Benzothiazoles; D004573:Electrolytes; D005456:Fluorescent Dyes; D011108:Polymers; D013844:Thiazoles; C473966:poly(phenylene ethynylene); C009462:thioflavin T; C421864:hen egg lysozyme; D009113:Muramidase
keywords: Alzheimer’s disease; J aggregates; amyloid diseases; amyloid fibril staining; conjugated oligoelectrolytes; fluorescent optical probes; protein aggregate detection