Hyperbranched polymers, Dopamine, Macromolecular crowding, Parkinson's disease, Protein aggregation, RAFT polymerization, α-synuclein, DOPAdopamine, dopamine, DPdopamine-containing polymer, dopamine-containing polymer, PEGpolyethylene glycol, polyethylene glycol, ThTthioflavin T, thioflavin T, RAFTreversible addition-fragmentation chain transfer, reversible addition-fragmentation chain transfer
Digital Object Identifier (DOI)
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.
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Citation / Publisher Attribution
Biochemical and Biophysical Research Communications, v. 469, issue 4, p. 830-835
Scholar Commons Citation
Breydo, Leonid; Newland, Ben; Zhang, Hong; Rosser, Anne; Werner, Carsten; Uversky, Vladimir N.; and Wang, Wenxin, "A Hyperbranched Dopamine-containing PEG-based Polymer for the Inhibition of Α-synuclein Fibrillation" (2016). Molecular Medicine Faculty Publications. 335.