Site-Specific Fluorescence Polarization for Studying the Disaggregation of α-Synuclein Fibrils by Small Molecules

被引：23

作者：

Haney, Conor M. ^{[1
]}

Cleveland, Christina L. ^{[1
]}

Wissner, Rebecca F. ^{[1
,4
]}

Owei, Lily ^{[1
]}

Robustelli, Jaclyn ^{[1
]}

Daniels, Malcolm J. ^{[2
]}

Canyurt, Merve ^{[1
,5
]}

Rodriguez, Priscilla ^{[1
]}

Ischiropoulos, Harry ^{[3
]}

Baumgart, Tobias ^{[1
]}

Petersson, E. James ^{[1
]}

机构：

[1] Univ Penn, Dept Chem, 231 South 34th St, Philadelphia, PA 19104 USA

[2] Univ Penn, Pharmacol Grad Grp, 3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA

[3] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA

[4] Yale Univ, Dept Chem, 225 Prospect St, New Haven, CT 06520 USA

[5] Bilkent Univ, Dept Chem, Fac Sci, TR-06800 Ankara, Turkey

来源：

BIOCHEMISTRY | 2017年 / 56卷 / 05期

基金：

美国国家卫生研究院;

关键词：

PARKINSONS-DISEASE; OXIDATION-PRODUCTS; AMYLOID FIBRILS; IN-VITRO; DOPAMINE; AGGREGATION; OLIGOMERS; AUTOXIDATION; TOXICITY; BETA;

D O I：

10.1021/acs.biochem.6b01060

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Fibrillar aggregates of the protein alpha-synuclein (alpha S) are one of the hallmarks of Parkinson's disease. Here, we show that measuring the fluorescence polarization (FP) of labels at several sites on aS allows one to monitor changes in the local dynamics of the protein after binding to micelles or vesicles, and during fibril formation. Most significantly, these site-specific FP measurements provide insight into structural remodeling of aS fibrils by small molecules and have the potential for use in moderate-throughput screens to identify small molecules that could be used to treat Parkinson's disease.

引用

页码：683 / 691

页数：9

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