Inhibition of a viral prolyl hydroxylase.

Enzyme Assays Hydroxylation Hypoxia-Inducible Factor-Proline Dioxygenases / chemistry Ketoglutaric Acids / chemistry Oligopeptides / chemistry Phycodnaviridae / enzymology Procollagen-Proline Dioxygenase / chemistry Prolyl-Hydroxylase Inhibitors / chemistry Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
2-Oxoglutarate Collagen biosynthesis Erythropoietin (EPO) Hypoxia inducible factor Prolyl hydroxylase inhibitor α-Ketoglutarate oxygenase

Journal

Bioorganic & medicinal chemistry
ISSN: 1464-3391
Titre abrégé: Bioorg Med Chem
Pays: England
ID NLM: 9413298

Informations de publication

Date de publication:
15 06 2019
Historique:
received: 14 11 2018
revised: 15 01 2019
accepted: 21 01 2019
pubmed: 10 2 2019
medline: 25 8 2020
entrez: 10 2 2019
Statut: ppublish

Résumé

The hydroxylation of prolyl-residues in eukaryotes is important in collagen biosynthesis and in hypoxic signalling. The hypoxia inducible factor (HIF) prolyl hydroxylases (PHDs) are drug targets for the treatment of anaemia, while the procollagen prolyl hydroxylases and other 2-oxoglutarate dependent oxygenases are potential therapeutic targets for treatment of cancer, fibrotic disease, and infection. We describe assay development and inhibition studies for a procollagen prolyl hydroxylase from Paramecium bursaria chlorella virus 1 (vCPH). The results reveal HIF PHD inhibitors in clinical trials also inhibit vCPH. Implications for the targeting of the human PHDs and microbial prolyl hydroxylases are discussed.

Identifiants

DOI: 10.1016/j.bmc.2019.01.018 PMID: 30737136
pubmed: 30737136
pii: S0968-0896(18)31936-9
doi: 10.1016/j.bmc.2019.01.018
pii:
doi:

Substances chimiques

Ketoglutaric Acids 0
Oligopeptides 0
Prolyl-Hydroxylase Inhibitors 0
Procollagen-Proline Dioxygenase EC 1.14.11.2
Hypoxia-Inducible Factor-Proline Dioxygenases EC 1.14.11.29

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2405-2412

Subventions

Organisme : British Heart Foundation
ID : PG/12/33/29546
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Cancer Research UK
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
Pays : United Kingdom

Informations de copyright

Copyright © 2019. Published by Elsevier Ltd.

Auteurs

Gareth W Langley (GW)

Chemistry Research Laboratory, Department of Chemistry, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, United Kingdom.

Martine I Abboud (MI)

Chemistry Research Laboratory, Department of Chemistry, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, United Kingdom.

Christopher T Lohans (CT)

Chemistry Research Laboratory, Department of Chemistry, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, United Kingdom.

Christopher J Schofield (CJ)

Chemistry Research Laboratory, Department of Chemistry, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, United Kingdom. Electronic address: Christopher.Schofield@chem.ox.ac.uk.

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Classifications MeSH

questionsmedicales.fr › Techniques d'investigation › Techniques de chimie analytique › Dosages enzymatiques › Inhibition of a viral prolyl hydroxylase.
questionsmedicales.fr › Métabolisme › Hydroxylation › Inhibition of a viral prolyl hydroxylase.
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Oxidoreductases › Oxygénases › Mixed function oxygenases › Prolyl hydroxylases › Hypoxia-inducible factor-proline dioxygenases › Inhibition of a viral prolyl hydroxylase.
questionsmedicales.fr › Composés chimiques organiques › Acides carboxyliques › Cétoacides › Acides cétoglutariques › Inhibition of a viral prolyl hydroxylase.
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Oligopeptides › Inhibition of a viral prolyl hydroxylase.
questionsmedicales.fr › Virus › Virus des plantes › Phycodnaviridae › Inhibition of a viral prolyl hydroxylase.
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Oxidoreductases › Oxygénases › Mixed function oxygenases › Prolyl hydroxylases › Procollagen-Proline Dioxygenase › Inhibition of a viral prolyl hydroxylase.
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antienzymes › Inhibiteurs de prolyle hydroxylases › Inhibition of a viral prolyl hydroxylase.
questionsmedicales.fr › Techniques d'investigation › Techniques de chimie analytique › Spectrométrie de masse › Spectrométrie de masse MALDI › Inhibition of a viral prolyl hydroxylase.