A Fluorescent Benzo[g]isoquinoline-Based HIF Prolyl Hydroxylase Inhibitor for Cellular Imaging.

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.

• Authors: Marleen Mayer, Kerstin Fey, Eva Heinze, Christian R Wick, Martine I Abboud, Tzu-Lan Yeh, Anthony Tumber, Nicole Orth, Gunnar Schley, Björn Buchholz, Timothy Clark, Christopher J Schofield, Carsten Willam, Nicolai Burzlaff
• Journal: ChemMedChem (ChemMedChem) Vol. 14 Issue 1 Pg. 94-99 (01 08 2019) ISSN: 1860-7187 [Electronic] Germany
• PMID: 30380199 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Benzylisoquinolines
• Fluorescent Dyes
• Prolyl-Hydroxylase Inhibitors
• Prolyl Hydroxylases

Topics

• Benzylisoquinolines (chemical synthesis, chemistry, pharmacology)
• Biocatalysis (drug effects)
• Dose-Response Relationship, Drug
• Fluorescent Dyes (chemical synthesis, chemistry, pharmacology)
• HeLa Cells
• Humans
• Molecular Imaging (methods)
• Molecular Structure
• Optical Imaging (methods)
• Prolyl Hydroxylases (metabolism)
• Prolyl-Hydroxylase Inhibitors (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship