Alpha Synuclein Fibrils Contain Multiple Binding Sites for Small Molecules

Chia Ju Hsieh, John J. Ferrie, Kuiying Xu, Iljung Lee, Thomas J.A. Graham, Zhude Tu, Jennifer Yu, Dhruva Dhavale, Paul Kotzbauer, E. James Petersson, Robert H. Mach

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

The fibrillary aggregation of the protein alpha synuclein (Asyn) is a hallmark of Parkinson's disease, and the identification of small molecule binding sites on fibrils is essential to the development of diagnostic imaging probes. A series of molecular modeling, photoaffinity labeling, mass spectrometry, and radioligand binding studies were conducted on Asyn fibrils. The results of these studies revealed the presence of three different binding sites within fibrillar Asyn capable of binding small molecules with moderate to high affinity. A knowledge of the amino acid residues in these binding sites will be important in the design of high affinity probes capable of imaging fibrillary species of Asyn.

Original languageEnglish
Pages (from-to)2521-2527
Number of pages7
JournalACS Chemical Neuroscience
Volume9
Issue number11
DOIs
StatePublished - Nov 21 2018

Keywords

  • Alpha synuclein
  • Lewy bodies
  • Lewy neurites
  • Parkinson's disease

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