1. A Fluorescent Benzo[g]isoquinoline-Based HIF Prolyl Hydroxylase Inhibitor for Cellular Imaging.
- Author
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Mayer M, Fey K, Heinze E, Wick CR, Abboud MI, Yeh TL, Tumber A, Orth N, Schley G, Buchholz B, Clark T, Schofield CJ, Willam C, and Burzlaff N
- Subjects
- Benzylisoquinolines chemical synthesis, Benzylisoquinolines chemistry, Biocatalysis drug effects, Dose-Response Relationship, Drug, Fluorescent Dyes chemical synthesis, Fluorescent Dyes chemistry, HeLa Cells, Humans, Molecular Structure, Prolyl-Hydroxylase Inhibitors chemical synthesis, Prolyl-Hydroxylase Inhibitors chemistry, Structure-Activity Relationship, Benzylisoquinolines pharmacology, Fluorescent Dyes pharmacology, Molecular Imaging methods, Optical Imaging methods, Prolyl Hydroxylases metabolism, Prolyl-Hydroxylase Inhibitors pharmacology
- Abstract
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., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2019
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