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dc.contributor.authorXu, Mingming
dc.contributor.authorLoa-Kum-Cheung, Wendy
dc.contributor.authorZhang, Haiyan
dc.contributor.authorQuinn, Ronald J
dc.contributor.authorMellick, George D
dc.date.accessioned2019-09-10T02:43:22Z
dc.date.available2019-09-10T02:43:22Z
dc.date.issued2019
dc.identifier.issn1948-7193
dc.identifier.doi10.1021/acschemneuro.9b00092
dc.identifier.urihttp://hdl.handle.net/10072/387157
dc.description.abstractThe aggregation of disordered α-synuclein protein is pathogenically connected with Parkinson’s disease. Therefore, discovering molecules that can inhibit the misfolding and aggregation of α-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 α-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 α-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 α-synuclein and protects neuroblastoma cells from α-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 α-synuclein aggregation and also consolidates the capability of mass spectrometry to discover α-synuclein aggregation inhibitors.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Chemical Society
dc.relation.ispartofpagefrom2683
dc.relation.ispartofpageto2691
dc.relation.ispartofissue6
dc.relation.ispartofjournalACS Chemical Neuroscience
dc.relation.ispartofvolume10
dc.subject.fieldofresearchMedicinal and Biomolecular Chemistry
dc.subject.fieldofresearchcode0304
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsBiochemistry & Molecular Biology
dc.subject.keywordsChemistry, Medicinal
dc.subject.keywordsNeurosciences
dc.titleIdentification of a New alpha-Synuclein Aggregation Inhibitor via Mass Spectrometry Based Screening
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationXu, M; Loa-Kum-Cheung, W; Zhang, H; Quinn, RJ; Mellick, GD, Identification of a New alpha-Synuclein Aggregation Inhibitor via Mass Spectrometry Based Screening, ACS Chemical Neuroscience, 2019, 10 (6), pp. 2683-2691
dc.date.updated2019-09-10T02:40:56Z
gro.hasfulltextNo Full Text
gro.griffith.authorMellick, George
gro.griffith.authorLoa-Kum-Cheung, Wendy
gro.griffith.authorQuinn, Ronald J.
gro.griffith.authorXu, Manny
gro.griffith.authorZhang, Haiyan


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