A Fluorescent Benzo[g]isoquinoline-Based HIF Prolyl Hydroxylase Inhibitor for Cellular Imaging.
Benzylisoquinolines
/ chemical synthesis
Biocatalysis
/ drug effects
Dose-Response Relationship, Drug
Fluorescent Dyes
/ chemical synthesis
HeLa Cells
Humans
Molecular Imaging
/ methods
Molecular Structure
Optical Imaging
/ methods
Prolyl Hydroxylases
/ metabolism
Prolyl-Hydroxylase Inhibitors
/ chemical synthesis
Structure-Activity Relationship
HIF system
PHD inhibitors
fluorescence microscopy
hypoxia
oxygen sensing
Journal
ChemMedChem
ISSN: 1860-7187
Titre abrégé: ChemMedChem
Pays: Germany
ID NLM: 101259013
Informations de publication
Date de publication:
08 01 2019
08 01 2019
Historique:
received:
21
07
2018
revised:
08
10
2018
pubmed:
1
11
2018
medline:
2
11
2019
entrez:
1
11
2018
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30380199
doi: 10.1002/cmdc.201800483
doi:
Substances chimiques
Benzylisoquinolines
0
Fluorescent Dyes
0
Prolyl-Hydroxylase Inhibitors
0
Prolyl Hydroxylases
EC 1.14.11.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
94-99Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/D011523/1
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/12/33/29546
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 106244/Z/14/Z
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C9047/A24759
Pays : United Kingdom
Informations de copyright
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.