Identification of a New alpha-Synuclein Aggregation Inhibitor via Mass Spectrometry Based Screening
文献类型：期刊论文
| 作者 | Xu, Mingming1; Loa-Kum-Cheung, Wendy1; Zhang, Haiyan2 ; Quinn, Ronald J.1; Mellick, George D.1
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| 刊名 | ACS CHEMICAL NEUROSCIENCE
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| 出版日期 | 2019-06-01 |
| 卷号 | 10期号:6页码:2683-2691 |
| 关键词 | Parkinson's disease alpha-synuclein aggregation mass spectrometry screening inhibitor |
| ISSN号 | 1948-7193 |
| DOI | 10.1021/acschemneuro.9b00092 |
| 通讯作者 | Quinn, Ronald J.(r.quinn@griffith.edu.au) ; Mellick, George D.(g.mellick@griffith.edu.au) |
| 英文摘要 | The aggregation of disordered alpha-synuclein protein is pathogenically connected with Parkinson's disease. Therefore, discovering molecules that can inhibit the misfolding and aggregation of alpha-synuclein is an active research area in PD drug development. A key property of such required therapeutic agents is specific binding to the target protein. Mass spectrometry allows rapid detection of direct interactions between molecules and proteins and is an ideal technique for discovering specific alpha-synuclein binders. Here, by setting up an automated mass spectrometry-based screening system, we were able to screen over 2500 compounds and identify a new alpha-synuclein inhibitor, 3-[(3-methoxyphenyl)carbamoyl]-7-[(E)-2-phenylethenyl]-4,7-dihydropyrazolo [1,5-a]pyrimidine-5-carboxylic acid (compound 2). This compound not only significantly inhibits the misfolding and aggregation of a-synuclein and protects neuroblastoma cells from alpha-synuclein toxicity, but also has a more specific binding site compared with positive controls. Our work for the first time reports the inhibition of compound 2 on alpha-synuclein aggregation and also consolidates the capability of mass spectrometry to discover alpha-synuclein aggregation inhibitors. |
| WOS关键词 | PARKINSONS-DISEASE ; BINDING ; OLIGOMERS |
| 资助项目 | Griffith University International Postgraduate Research Scholarship (GUIPRS) ; Griffith University Postgraduate Research Scholarship (GUPRS) ; Australian Research Council[LE 120100170] ; Griffith University |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Neurosciences & Neurology |
| 语种 | 英语 |
| WOS记录号 | WOS:000472678800008 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/289241]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Quinn, Ronald J.; Mellick, George D. |
| 作者单位 | 1.Griffith Univ, Griffith Inst Drug Discovery, Don Young Rd, Nathan, Qld 4111, Australia 2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xu, Mingming,Loa-Kum-Cheung, Wendy,Zhang, Haiyan,et al. Identification of a New alpha-Synuclein Aggregation Inhibitor via Mass Spectrometry Based Screening[J]. ACS CHEMICAL NEUROSCIENCE,2019,10(6):2683-2691. |
| APA | Xu, Mingming,Loa-Kum-Cheung, Wendy,Zhang, Haiyan,Quinn, Ronald J.,&Mellick, George D..(2019).Identification of a New alpha-Synuclein Aggregation Inhibitor via Mass Spectrometry Based Screening.ACS CHEMICAL NEUROSCIENCE,10(6),2683-2691. |
| MLA | Xu, Mingming,et al."Identification of a New alpha-Synuclein Aggregation Inhibitor via Mass Spectrometry Based Screening".ACS CHEMICAL NEUROSCIENCE 10.6(2019):2683-2691. |
入库方式： OAI收割
来源：上海药物研究所
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