title: Novel intramolecular photoinduced electron transfer-based probe for the Human Ether-a-go-go-Related Gene (hERG) potassium channel.
abstract: Drug induced long QT syndrome is a high risk event in clinic, which mainly results from their high affinity to the Human Ether-a-go-go-Related Gene (hERG) potassium channel. Therefore, evaluation of the drug's inhibitory activity against the hERG potassium channel is a required step in drug discovery and development. In this study, we developed a series of novel conformation-mediated intramolecular photoinduced electron transfer fluorogenic probes for the hERG potassium channel. After careful evaluation, probes N4 and N6 showed good activity and may have a promising application in the cell-based hERG potassium channel inhibitory activity assay, as well as potential hERG-associated cardiotoxicity evaluation. Compared with other assay methods, such as patch clamp assay, radio-ligand competitive binding assay, fluorescence polarization and potential-sensitive fluorescent probes, this method is convenient and can also selectively measure the inhibitory activity in the native state of the hERG potassium channel. Meanwhile, these probes can also be used for hERG potassium channel imaging without complex washing steps.
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology of Natural Products (MOE), School of Pharmacy, Shandong University, Jinan, Shandong 250012, China. dulupei@sdu.edu.cn mli@sdu.edu.cn.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Institute of Biosciences & Technology, Texas A&M University Health Science Center, Houston, TX 77030, USA.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology of Natural Products (MOE), School of Pharmacy, Shandong University, Jinan, Shandong 250012, China. dulupei@sdu.edu.cn mli@sdu.edu.cn.
authors.forename: Lupei
authors.initials: L
authors.lastname: Du
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology of Natural Products (MOE), School of Pharmacy, Shandong University, Jinan, Shandong 250012, China. dulupei@sdu.edu.cn mli@sdu.edu.cn.
authors.forename: Minyong
authors.initials: M
authors.lastname: Li
mesh_terms: D001681:Biological Assay / Q000295:instrumentation*; D004579:Electron Transport; D004583:Electrons; D051638:Ether-A-Go-Go Potassium Channels / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry*; D057809:HEK293 Cells; D006801:Humans; D008027:Light; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D015394:Molecular Structure
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; D005456:Fluorescent Dyes