Department of Chemistry and Pharmacy, Inorganic and Organometallic Chemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg, Egerlandstraße 1, 91058, Erlangen, Germany.
Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg, Ulmenweg 18, 91054, Erlangen, Germany.
ChemMedChem. 2019 Jan 8;14(1):94-99. doi: 10.1002/cmdc.201800483. Epub 2018 Dec 21.
Prolyl hydroxylation domain (PHD) enzymes catalyze the hydroxylation of the transcription factor hypoxia-inducible factor (HIF) and serve as cellular oxygen sensors. HIF and the PHD enzymes regulate numerous potentially tissue-protective target genes which can adapt cells to metabolic and ischemic stress. We describe a fluorescent PHD inhibitor (1-chloro-4-hydroxybenzo[g]isoquinoline-3-carbonyl)glycine which is suited to fluorescence-based detection assays and for monitoring PHD inhibitors in biological systems. In cell-based assays, application of the fluorescent PHD inhibitor allowed co-localization with a cellular PHD enzyme and led to live cell imaging of processes involved in cellular oxygen sensing.
脯氨酰羟化酶结构域 (PHD) 酶催化转录因子缺氧诱导因子 (HIF) 的羟化作用，充当细胞氧传感器。HIF 和 PHD 酶调节许多潜在的组织保护靶基因，使细胞能够适应代谢和缺血应激。我们描述了一种荧光 PHD 抑制剂（1-氯-4-羟基苯并[g]异喹啉-3-甲酰基）甘氨酸，它适合荧光检测分析，并可用于监测生物系统中的 PHD 抑制剂。在基于细胞的测定中，荧光 PHD 抑制剂的应用允许与细胞 PHD 酶共定位，并导致细胞氧感应相关过程的活细胞成像。
