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Construction of a Fluorescent Screening System of Allosteric Modulators for the GABAA Receptor Using a Turn-On Probe
https://repo.qst.go.jp/records/76654
https://repo.qst.go.jp/records/766549f833d5d-0b7f-4684-bb19-e8ca9d0d43bc
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2019-09-04 | |||||
| タイトル | ||||||
| タイトル | Construction of a Fluorescent Screening System of Allosteric Modulators for the GABAA Receptor Using a Turn-On Probe | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Sakamoto, Seiji
× Sakamoto, Seiji× Yamaura, Kei× Numata, Tomohiro× Harada, Fumio× Amaike, Kazuma× Inoue, Ryuji× Kiyonaka, Shigeki× Hamachi, Itaru× Kei, Yamaura |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system. The fast inhibitory actions of GABA are mainly mediated by GABAA receptors (GABAARs), which are widely recognized as clinically relevant drug targets. However, it remains difficult to create screening systems for drug candidates that act on GABAARs because of the existence of multiple ligand-binding sites and the delicate pentameric structures of GABAARs. We here developed the first turn-on fluorescent imaging probe for GABAARs, which can be used to quantitatively evaluate ligand–receptor interactions under live cell conditions. Using noncovalent labeling of GABAARs with this turn-on probe, a new imaging-based ligand assay system, which allows discovery of positive allosteric modulators (PAMs) for the GABAAR, was successfully constructed. Our system is applicable to high-throughput ligand screening, and we discovered new small molecules that function as PAMs for GABAARs. These results highlight the power of the use of a turn-on fluorescent probe to screen drugs for complicated membrane proteins that cannot be addressed by conventional methods. | |||||
| 書誌情報 |
ACS Central Science 巻 5, 号 9, p. 1541-1553, 発行日 2019-08 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 2374-7943 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1021/acscentsci.9b00539 | |||||
| 関連サイト | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.1021/acscentsci.9b00539 | |||||
