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Alpha Synuclein Fibrils Contain Multiple Binding Sites for Small Molecules.

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.

SUBMITTER: Hsieh CJ

PROVIDER: S-EPMC6736640 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Alpha Synuclein Fibrils Contain Multiple Binding Sites for Small Molecules.

Hsieh Chia-Ju CJ Ferrie John J JJ Xu Kuiying K Lee Iljung I Graham Thomas J A TJA Tu Zhude Z Yu Jennifer J Dhavale Dhruva D Kotzbauer Paul P Petersson E James EJ Mach Robert H RH

ACS chemical neuroscience 20180516 11

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 ...[more]

PMID: 29750499

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