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

Breydo, Leonid, Newland, Benjamin, Zhang, Hong, Rosser, Anne Elizabeth, Werner, Carsten, Uversky, Vladimir N. and Wang, Wenxin 2016. A hyperbranched dopamine-containing PEG-based polymer for the inhibition of a-synuclein fibrillation. Biochemical and Biophysical Research Communications 469 (4) , pp. 830-835. 10.1016/j.bbrc.2015.12.060

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Neuroscience and Mental Health Research Institute (NMHRI)
Pharmacy
Publisher: Elsevier
ISSN: 0006-291X
Funders: Wellcome
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 15 December 2015
Last Modified: 15 Dec 2017 11:46
URI: http://orca.cf.ac.uk/id/eprint/84563

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