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A Fluorescent Benzo[ g ]isoquinoline‐Based HIF Prolyl Hydroxylase Inhibitor for Cellular Imaging
Author(s) -
Mayer Marleen,
Fey Kerstin,
Heinze Eva,
Wick Christian R.,
Abboud Martine I.,
Yeh TzuLan,
Tumber Anthony,
Orth Nicole,
Schley Gunnar,
Buchholz Björn,
Clark Timothy,
Schofield Christopher J.,
Willam Carsten,
Burzlaff Nicolai
Publication year - 2019
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201800483
Subject(s) - hydroxylation , isoquinoline , enzyme , chemistry , biochemistry , fluorescence , hypoxia inducible factors , transcription factor , green fluorescent protein , hypoxia inducible factor 1 , microbiology and biotechnology , stereochemistry , biology , gene , physics , quantum mechanics
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.