title: Site-Specific Fluorescence Polarization for Studying the Disaggregation of α-Synuclein Fibrils by Small Molecules.
abstract: Fibrillar aggregates of the protein α-synuclein (αS) are one of the hallmarks of Parkinson's disease. Here, we show that measuring the fluorescence polarization (FP) of labels at several sites on αS allows one to monitor changes in the local dynamics of the protein after binding to micelles or vesicles, and during fibril formation. Most significantly, these site-specific FP measurements provide insight into structural remodeling of αS fibrils by small molecules and have the potential for use in moderate-throughput screens to identify small molecules that could be used to treat Parkinson's disease.
authors.affiliation: Department of Chemistry, University of Pennsylvania , 231 South 34th Street, Philadelphia, Pennsylvania 19104, United States.
authors.forename: Conor M
authors.initials: CM
authors.lastname: Haney
authors.affiliation: Department of Chemistry, University of Pennsylvania , 231 South 34th Street, Philadelphia, Pennsylvania 19104, United States.
authors.forename: Christina L
authors.initials: CL
authors.lastname: Cleveland
authors.affiliation: Department of Chemistry, University of Pennsylvania , 231 South 34th Street, Philadelphia, Pennsylvania 19104, United States.
authors.forename: Rebecca F
authors.initials: RF
authors.lastname: Wissner
authors.affiliation: Department of Chemistry, University of Pennsylvania , 231 South 34th Street, Philadelphia, Pennsylvania 19104, United States.
authors.forename: Lily
authors.initials: L
authors.lastname: Owei
authors.affiliation: Department of Chemistry, University of Pennsylvania , 231 South 34th Street, Philadelphia, Pennsylvania 19104, United States.
authors.forename: Jaclyn
authors.initials: J
authors.lastname: Robustelli
authors.affiliation: Pharmacology Graduate Group, University of Pennsylvania , 3400 Civic Center Boulevard, Philadelphia, Pennsylvania 19104, United States.
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Daniels
authors.affiliation: Department of Chemistry, University of Pennsylvania , 231 South 34th Street, Philadelphia, Pennsylvania 19104, United States.
authors.forename: Merve
authors.initials: M
authors.lastname: Canyurt
authors.affiliation: Department of Chemistry, University of Pennsylvania , 231 South 34th Street, Philadelphia, Pennsylvania 19104, United States.
authors.forename: Priscilla
authors.initials: P
authors.lastname: Rodriguez
authors.affiliation: Department of Pediatrics, Children's Hospital of Philadelphia , Philadelphia, Pennsylvania 19104, United States.
authors.forename: Harry
authors.initials: H
authors.lastname: Ischiropoulos
authors.affiliation: Department of Chemistry, University of Pennsylvania , 231 South 34th Street, Philadelphia, Pennsylvania 19104, United States.
authors.forename: Tobias
authors.initials: T
authors.lastname: Baumgart
authors.affiliation: Department of Chemistry, University of Pennsylvania , 231 South 34th Street, Philadelphia, Pennsylvania 19104, United States.
authors.forename: E James
authors.initials: EJ
authors.lastname: Petersson
mesh_terms: D000595:Amino Acid Sequence; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004298:Dopamine / Q000737:chemistry* / Q000494:pharmacology; D005454:Fluorescence Polarization; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D009637:Masoprocol / Q000737:chemistry* / Q000378:metabolism; D010713:Phosphatidylcholines / Q000737:chemistry; D066329:Protein Aggregates / Q000187:drug effects*; D011994:Recombinant Proteins / Q000737:chemistry; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D053835:Unilamellar Liposomes / Q000737:chemistry; D014966:Xanthenes / Q000737:chemistry; D051844:alpha-Synuclein / Q000737:chemistry*
chemical_list: D005456:Fluorescent Dyes; D010713:Phosphatidylcholines; D066329:Protein Aggregates; D011994:Recombinant Proteins; D054852:Small Molecule Libraries; D053835:Unilamellar Liposomes; D014966:Xanthenes; D051844:alpha-Synuclein; D012967:Sodium Dodecyl Sulfate; D009637:Masoprocol; C034657:Texas red; D002392:Catechin; C045651:epigallocatechin gallate; C017251:1,2-oleoylphosphatidylcholine; D004298:Dopamine