title: The broad spectrum 2-oxoglutarate oxygenase inhibitor N-oxalylglycine is present in rhubarb and spinach leaves.
abstract: 2-Oxoglutarate (2OG) and ferrous iron dependent oxygenases are involved in many biological processes in organisms ranging from humans (where some are therapeutic targets) to plants. These enzymes are of significant biomedicinal interest because of their roles in hypoxic signaling and epigenetic regulation. Synthetic N-oxalylglycine (NOG) has been identified as a broad-spectrum 2OG oxygenase inhibitor and is currently widely used in studies on the hypoxic response and chromatin modifications in animals. We report the identification of NOG as a natural product present in Rheum rhabarbarum (rhubarb) and Spinach oleracea (spinach) leaves; NOG was not observed in Escherchia coli or human embryonic kidney cells (HEK 293T). The finding presents the possibility that NOG plays a natural role in regulating gene expression by inhibiting 2OG dependent oxygenases. This has significance because tricarboxylic acid cycle (TCA) intermediate inhibition of 2OG dependent oxygenases has attracted major interest in cancer research.
authors.affiliation: Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford OX1 3TA, United Kingdom; Metabolic Screening Laboratory, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia.
authors.forename: Khalid
authors.initials: K
authors.lastname: Al-Qahtani
authors.affiliation: Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford OX1 3TA, United Kingdom; Department of Chemistry, Baghdad-ul-Jadeed Campus, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
authors.forename: Bushra
authors.initials: B
authors.lastname: Jabeen
authors.affiliation: Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford OX1 3TA, United Kingdom.
authors.forename: Rok
authors.initials: R
authors.lastname: Sekirnik
authors.affiliation: Department of Chemistry, Baghdad-ul-Jadeed Campus, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
authors.forename: Naheed
authors.initials: N
authors.lastname: Riaz
authors.affiliation: Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford OX1 3TA, United Kingdom.
authors.forename: Timothy D W
authors.initials: TDW
authors.lastname: Claridge
authors.affiliation: Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford OX1 3TA, United Kingdom.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Schofield
authors.affiliation: Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford OX1 3TA, United Kingdom. Electronic address: james.mccullagh@chem.ox.ac.uk.
authors.forename: James S O
authors.initials: JSO
authors.lastname: McCullagh
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification; D000600:Amino Acids, Dicarboxylic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001937:Brassica / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology; D004926:Escherichia coli / Q000737:chemistry; D057809:HEK293 Cells / Q000737:chemistry; D006801:Humans; D007656:Ketoglutaric Acids / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D010105:Oxygenases / Q000037:antagonists & inhibitors; D018515:Plant Leaves / Q000737:chemistry*; D012250:Rheum / Q000737:chemistry*; D018724:Spinacia oleracea / Q000737:chemistry*; D053719:Tandem Mass Spectrometry
chemical_list: D000600:Amino Acids, Dicarboxylic; D004791:Enzyme Inhibitors; D007656:Ketoglutaric Acids; D010105:Oxygenases; D000409:Alanine; C040947:oxalylglycine
keywords: Amino acid; Inhibitor; N-oxalylglycine; Natural product; Oxygenases; Rheum rhabarbarum (rhubarb); Spinach oleracea (spinach)