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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.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1002/cmdc.201800483

Authors


More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Sub department:
Organic Chemistry
Role:
Author
ORCID:
0000-0003-2141-5988


More from this funder
Funding agency for:
Abboud, M
Schofield, C
Grant:
18245
18245
More from this funder
Funding agency for:
Abboud, M
Schofield, C
Grant:
18245
18245


Publisher:
Wiley
Journal:
ChemMedChem More from this journal
Volume:
14
Issue:
1
Pages:
94-99
Publication date:
2018-12-21
Acceptance date:
2018-10-26
DOI:
EISSN:
1860-7187
ISSN:
1860-7179


Keywords:
Pubs id:
pubs:935986
UUID:
uuid:09c12867-94e2-435e-b6b3-79cae589126b
Local pid:
pubs:935986
Source identifiers:
935986
Deposit date:
2018-11-01

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