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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Leonid Breydo - , University of South Florida (Author)
  • Ben Newland - , Leibniz Institute of Polymer Research Dresden, Cardiff University (Author)
  • Hong Zhang - , University College Dublin (Author)
  • Anne Rosser - , Cardiff University (Author)
  • Carsten Werner - , Chair of Biofunctional Polymer Materials, Leibniz Institute of Polymer Research Dresden (Author)
  • Vladimir N. Uversky - , University of South Florida, Russian Academy of Sciences, King Abdulaziz University (Author)
  • Wenxin Wang - , University College Dublin, Tianjin University (Author)

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

Original languageEnglish
Pages (from-to)830-835
Number of pages6
JournalBiochemical and biophysical research communications
Volume469
Issue number4
Publication statusPublished - 22 Jan 2016
Peer-reviewedYes

External IDs

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

Keywords

Keywords

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