A hyperbranched dopamine-containing PEG-based polymer for the inhibition of α-synuclein fibrillation

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Leonid Breydo - , University of South Florida (Autor:in)
  • Ben Newland - , Leibniz-Institut für Polymerforschung Dresden, Cardiff University (Autor:in)
  • Hong Zhang - , University College Dublin (Autor:in)
  • Anne Rosser - , Cardiff University (Autor:in)
  • Carsten Werner - , Professur für Biofunktionale Polymermaterialien (gB/IPF), Leibniz-Institut für Polymerforschung Dresden (Autor:in)
  • Vladimir N. Uversky - , University of South Florida, Russian Academy of Sciences, King Abdulaziz University (Autor:in)
  • Wenxin Wang - , University College Dublin, Tianjin University (Autor:in)

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.

Details

OriginalspracheEnglisch
Seiten (von - bis)830-835
Seitenumfang6
FachzeitschriftBiochemical and biophysical research communications
Jahrgang469
Ausgabenummer4
PublikationsstatusVeröffentlicht - 22 Jan. 2016
Peer-Review-StatusJa

Externe IDs

PubMed 26707645
ORCID /0000-0003-0189-3448/work/161890442

Schlagworte

Schlagwörter

  • Dopamine, Hyperbranched polymers, Macromolecular crowding, Parkinson's disease, Protein aggregation, RAFT polymerization, α-synuclein