title: A hyperbranched dopamine-containing PEG-based polymer for the inhibition of α-synuclein fibrillation.
abstract: Aggregation of α-synuclein is believed to play an important role in Parkinson's disease and in other neurodegenerative maladies. Small molecule inhibitors of this process are among the most promising drug candidates for neurodegenerative diseases. Dendrimers have also been studied for anti-fibrillation applications but they can be difficult and expensive to synthetize. Here we show that RAFT polymerization can be used to produce a hyperbranched polyethylene glycol structure via a one-pot reaction. This polymer included a dopamine moiety, a known inhibitor of α-synuclein fibril formation. Dopamine within the polymer structure was capable of aggregation inhibition, although not to the same degree as free dopamine. This result opens up new avenues for the use of controlled radical polymerizations as a means of preparing hyperbranched polymers for anti-fibrillation activity, but shows that the incorporation of functional groups from known small molecules within polymers may alter their biological activity.
authors.affiliation: Department of Molecular Medicine and Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, 33612 Tampa, FL, USA. Electronic address: lbreydo@health.usf.edu.
authors.forename: Leonid
authors.initials: L
authors.lastname: Breydo
authors.affiliation: Leibniz-Institute für Polymerforschung, Dresden, Germany; Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, UK.
authors.forename: Ben
authors.initials: B
authors.lastname: Newland
authors.affiliation: The Charles Institute of Dermatology, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Rosser
authors.affiliation: Leibniz-Institute für Polymerforschung, Dresden, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Werner
authors.affiliation: Department of Molecular Medicine and Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, 33612 Tampa, FL, USA; Institute for Biological Instrumentation, Russian Academy of Sciences, 142292 Pushchino, Moscow Region, Russia; Department of Biological Sciences, Faculty of Science, King Abdulaziz University, PO Box 80203, 21589 Jeddah, Saudi Arabia.
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Uversky
authors.affiliation: The Charles Institute of Dermatology, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland; School of Materials Science and Engineering, Tianjin University, Tianjin, China.
authors.forename: Wenxin
authors.initials: W
authors.lastname: Wang
mesh_terms: D000682:Amyloid / Q000138:chemical synthesis*; D019281:Dimerization; D004298:Dopamine / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods; D011092:Polyethylene Glycols / Q000737:chemistry*; D011485:Protein Binding; D051844:alpha-Synuclein / Q000737:chemistry*
chemical_list: D000682:Amyloid; D051844:alpha-Synuclein; D011092:Polyethylene Glycols; D004298:Dopamine
keywords: Dopamine; Hyperbranched polymers; Macromolecular crowding; Parkinson's disease; Protein aggregation; RAFT polymerization; α-synuclein