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Christopher J. Schofield

Christopher Joseph Schofield (also known as Chris Schofield) is a Professor of Chemistry at the University of Oxford[1] and a Fellow of the Royal Society. Chris Schofield is a professor of organic chemistry at the University of Oxford, Department of Chemistry[2] and a Fellow of Hertford College.[3] Schofield studied functional, structural and mechanistic understanding of enzymes that employ oxygen and 2-oxoglutarate as a co-substrate.[4] His work has opened up new possibilities in antibiotic research,[5] oxygen sensing,[6] and gene regulation.[7]

After work on plant and microbial oxygenases,[4] he studied uncharacterised human oxygenases.[8] His research has identified unanticipated roles for oxygenases[9] in regulating gene expression, importantly in the cellular hypoxic response,[10] and has revealed new post-translational modifications to chromatin and RNA splicing proteins.[11] The work has identified new opportunities for medicinal intervention.[12]

Education

Chris Schofield attended St Anselm's College catholic grammar school in Merseyside, then studied for a Bachelor of Science in chemistry at the University of Manchester and graduated with a first class honour (1979–1982). In 1982, he moved to Oxford to study for a DPhil with Professor Jack E. Baldwin. In 1985, he became a Departmental Demonstrator in the Dyson Perrins Laboratory, Oxford University followed by his appointment as a Lecturer in Chemistry[2] and a Fellow of Hertford College[3] in 1990. In 1998, he became professor of Chemistry,[1] and in 2011 he was appointed the Head of Organic Chemistry[13] at the Department of Chemistry, University of Oxford. In 2013, he was elected a Fellow of the Royal Society, FRS.[14]

Research

The work in laboratory of Chris Schofield focuses on different areas of research, including:

Molecular Mechanisms of the Hypoxic Response

Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric α,β-transcriptional complex[15] that mediates the cellular response to oxygen availability in multi-cellular organisms,[6][16] ranging from the simplest known animal Trichoplax adhaerens to humans.[4][6][17][18][19] Investigating the structures and mechanisms of the HIF prolyl hydroxylases is a current focus of the work.[10][20] The group solved crystal structures of PHD2[9][21] - one of the human prolyl hydroxylases - and discovered that the HIF asparaginyl hydroxylase also catalyses hydroxylation of conserved motifs,[22] the ankyrin repeat domain.

Chemical Basis of Epigenetics

A current focus of the group is modification of histones, in particular oxygenase catalysed N-demethylation of histone methylated-lysine residues[7][23] – in collaboration with the Structural Genomics Consortium. The histone demethylases[24][25] are of interest both with respect to their links to diseases, including cancer[26][27] and inflammatory diseases,[28] as well as the role of methylation in transcriptional regulation.[29] Recent areas of interest include the fat mass and obesity protein[30][31] which was shown to be a nucleic acid demethylase[32] and JMJD6[33][34] which is a lysyl hydroxylase modifying RNA splicing protein.[11]

Structural and Functional Studies on 2OG Oxygenases

The 2-oxoglutarate (2OG)-dependent oxygenases are a superfamily of non-haem iron dependent oxygenases,[35] most of which use the Krebs cycle intermediate, 2OG, as a co-substrate.[36] The group are interested in understanding these enzymes[37] for their ability to catalyse synthetically difficult or 'impossible' reactions (e.g. the stereoselective hydroxylation of unactivated carbon-hydrogen bonds), for their diverse physiological roles,[8] and for their links to disease.[38] The research focuses on members of the family that are linked to disease, or can be targeted for the treatment of disease.[39][40] Techniques involved in this interdisciplinary research include proteomics,[41] X-ray crystallography,[42] nuclear magnetic resonance (NMR) spectroscopy,[43][44][45][46][47] biological mass spectrometry,[48] molecular biology,[49] enzyme kinetics,[50][51] protein-directed dynamic combinatorial chemistry[52][53] and organic synthesis/medicinal chemistry.[54][55]

Antibiotics: Biosynthesis and Resistance Mechanisms

Most clinically used antibiotics are based upon natural products.[5] The most important family of antibiotics contains a β-lactam ring, and includes the penicillin,[56] cephalosporin, clavam,[57] and carbapenem[58] antibiotics. The group's biosynthetic work has focused on the clavams[59] and carbapenems,[58] with a particular focus being on the mechanism and structures of enzymes that catalyse chemically 'interesting' steps.[60][61] The biggest threat to the continued use of β-lactam antibiotics is that of bacterial resistance. Schofield is currently working on the design and synthesis of enzyme inhibitors[62][63][64][65] for the metallo β-lactamases[66] – there are no clinically used inhibitor[67] of these enzymes but they pose a significant threat as they catalyse the hydrolysis of almost all clinically used β-lactam antibiotics.[68] A particular interest involves human metallo β-lactamases which share the same fold.[69]

Awards and honours

2015-2020: Wellcome Trust Advanced Investigator Award (with Sir Peter Ratcliffe)

2013: Fellow of the Royal Society (London);[14] Member of EMBO; Fellow of the Royal Society of Biology, UK; Member of the Biochemical Society; Member of the Society for Experimental Biology, UK

2012: Finalist – Biotechnology and Biological Sciences Research Council 'Innovator of the Year'[70]

2011: Royal Society of Chemistry, Jeremy Knowles Award, UK;[71] Highly cited paper awards (e.g. Biochemical Journal, Bioorganic & Medicinal Chemistry Letters)

2009 – 2014: PI of ERC Advanced Investigator Grant SPA GA 2008 233240 (with Sir Peter Ratcliffe); Molecular Mechanism of Oxygen Sensing by Enzymes (MOOSE)

2000: Fellow of the Royal Society of Chemistry (London)

References

  1. ^ a b "Christopher Schofield". University of Oxford. Retrieved 24 July 2023.
  2. ^ a b "Home – Schofield Group". University of Oxford. Retrieved 8 August 2016.
  3. ^ a b "Professor Chris Schofield FRS | Hertford College". University of Oxford. Retrieved 8 August 2016.
  4. ^ a b c Chowdhury, Rasheduzzaman; Sekirnik, Rok; Brissett, Nigel C.; Krojer, Tobias; Ho, Chia-hua; Ng, Stanley S.; Clifton, Ian J.; Ge, Wei; Kershaw, Nadia J. (19 June 2014). "Ribosomal oxygenases are structurally conserved from prokaryotes to humans". Nature. 510 (7505): 422–426. Bibcode:2014Natur.510..422C. doi:10.1038/nature13263. ISSN 0028-0836. PMC 4066111. PMID 24814345.
  5. ^ a b Hamed, Refaat B.; Gomez-Castellanos, J. Ruben; Henry, Luc; Ducho, Christian; McDonough, Michael A.; Schofield, Christopher J. (10 December 2012). "The enzymes of β-lactam biosynthesis". Natural Product Reports. 30 (1): 21–107. doi:10.1039/C2NP20065A. ISSN 1460-4752. PMID 23135477.
  6. ^ a b c Schofield, Christopher J.; Ratcliffe, Peter J. (1 May 2004). "Oxygen sensing by HIF hydroxylases". Nature Reviews Molecular Cell Biology. 5 (5): 343–354. doi:10.1038/nrm1366. ISSN 1471-0072. PMID 15122348. S2CID 6586977.
  7. ^ a b Thinnes, Cyrille C.; England, Katherine S.; Kawamura, Akane; Chowdhury, Rasheduzzaman; Schofield, Christopher J.; Hopkinson, Richard J. (1 December 2014). "Targeting histone lysine demethylases – Progress, challenges, and the future". Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. Methylation: A Multifaceted Modification – looking at transcription and beyond. 1839 (12): 1416–1432. doi:10.1016/j.bbagrm.2014.05.009. PMC 4316176. PMID 24859458.
  8. ^ a b Horita, Shoichiro; Scotti, John S.; Thinnes, Cyrille; Mottaghi-Taromsari, Yousef S.; Thalhammer, Armin; Ge, Wei; Aik, WeiShen; Loenarz, Christoph; Schofield, Christopher J. (7 April 2015). "Structure of the Ribosomal Oxygenase OGFOD1 Provides Insights into the Regio- and Stereoselectivity of Prolyl Hydroxylases". Structure. 23 (4): 639–652. doi:10.1016/j.str.2015.01.014. PMC 4396695. PMID 25728928.
  9. ^ a b Chowdhury, R; McDonough, MA; Mecinović, J; Loenarz, C; Flashman, E; Hewitson, KS; Domene, C; Schofield, CJ (July 2009). "Structural Basis for Binding of Hypoxia-Inducible Factor to the Oxygen-Sensing Prolyl Hydroxylases". Structure. 17 (7): 981–989. doi:10.1016/j.str.2009.06.002. PMID 19604478.
  10. ^ a b Hon, Wai-Ching; Wilson, Michael I.; Harlos, Karl; Claridge, Timothy D. W.; Schofield, Christopher J.; Pugh, Christopher W.; Maxwell, Patrick H.; Ratcliffe, Peter J.; Stuart, David I. (27 June 2002). "Structural basis for the recognition of hydroxyproline in HIF-1α by pVHL". Nature. 417 (6892): 975–978. Bibcode:2002Natur.417..975H. doi:10.1038/nature00767. ISSN 0028-0836. PMID 12050673. S2CID 4388644.
  11. ^ a b Webby, Celia J.; Wolf, Alexander; Gromak, Natalia; Dreger, Mathias; Kramer, Holger; Kessler, Benedikt; Nielsen, Michael L.; Schmitz, Corinna; Butler, Danica S. (3 July 2009). "Jmjd6 Catalyses Lysyl-Hydroxylation of U2AF65, a Protein Associated with RNA Splicing". Science. 325 (5936): 90–93. Bibcode:2009Sci...325...90W. doi:10.1126/science.1175865. hdl:10033/78493. ISSN 0036-8075. PMID 19574390. S2CID 38938528.
  12. ^ "ReOx Ltd - Oxford Spin-out to Develop New Drug Therapies". Retrieved 8 August 2016.
  13. ^ "SELECTBIO – Epigenetics Speaker Biography". SELECTBIO. Retrieved 8 August 2016.
  14. ^ a b "Christopher Schofield". royalsociety.org. Retrieved 8 August 2016.
  15. ^ Wilkins, Sarah E.; Abboud, Martine I.; Hancock, Rebecca L.; Schofield, Christopher J. (19 April 2016). "Targeting Protein–Protein Interactions in the HIF System". ChemMedChem. 11 (8): 773–786. doi:10.1002/cmdc.201600012. ISSN 1860-7187. PMC 4848768. PMID 26997519.
  16. ^ Jaakkola, Panu; Mole, David R.; Tian, Ya-Min; Wilson, Michael I.; Gielbert, Janine; Gaskell, Simon J.; Kriegsheim, Alexander von; Hebestreit, Holger F.; Mukherji, Mridul (20 April 2001). "Targeting of HIF-α to the von Hippel-Lindau Ubiquitylation Complex by O2-Regulated Prolyl Hydroxylation". Science. 292 (5516): 468–472. Bibcode:2001Sci...292..468J. doi:10.1126/science.1059796. ISSN 0036-8075. PMID 11292861. S2CID 20914281.
  17. ^ Epstein, Andrew C. R.; Gleadle, Jonathan M.; McNeill, Luke A.; Hewitson, Kirsty S.; O'Rourke, John; Mole, David R.; Mukherji, Mridul; Metzen, Eric; Wilson, Michael I. (5 October 2001). "C. elegans EGL-9 and Mammalian Homologs Define a Family of Dioxygenases that Regulate HIF by Prolyl Hydroxylation". Cell. 107 (1): 43–54. doi:10.1016/S0092-8674(01)00507-4. PMID 11595184.
  18. ^ Ge, Wei; Wolf, Alexander; Feng, Tianshu; Ho, Chia-hua; Sekirnik, Rok; Zayer, Adam; Granatino, Nicolas; Cockman, Matthew E.; Loenarz, Christoph (1 December 2012). "Oxygenase-catalyzed ribosome hydroxylation occurs in prokaryotes and humans". Nature Chemical Biology. 8 (12): 960–962. doi:10.1038/nchembio.1093. ISSN 1552-4450. PMC 4972389. PMID 23103944.
  19. ^ Tian, Ya-Min; Yeoh, Kar Kheng; Lee, Myung Kyu; Eriksson, Tuula; Kessler, Benedikt M.; Kramer, Holger B.; Edelmann, Mariola J.; Willam, Carsten; Pugh, Christopher W. (15 April 2011). "Differential Sensitivity of Hypoxia Inducible Factor Hydroxylation Sites to Hypoxia and Hydroxylase Inhibitors". Journal of Biological Chemistry. 286 (15): 13041–13051. doi:10.1074/jbc.M110.211110. ISSN 0021-9258. PMC 3075650. PMID 21335549.
  20. ^ Loenarz, Christoph; Schofield, Christopher J. (1 March 2008). "Expanding chemical biology of 2-oxoglutarate oxygenases". Nature Chemical Biology. 4 (3): 152–156. doi:10.1038/nchembio0308-152. ISSN 1552-4450. PMID 18277970.
  21. ^ McDonough, Michael A.; Li, Vivian; Flashman, Emily; Chowdhury, Rasheduzzaman; Mohr, Christopher; Liénard, Benoît M. R.; Zondlo, James; Oldham, Neil J.; Clifton, Ian J. (27 June 2006). "Cellular oxygen sensing: Crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2)". Proceedings of the National Academy of Sciences. 103 (26): 9814–9819. Bibcode:2006PNAS..103.9814M. doi:10.1073/pnas.0601283103. ISSN 0027-8424. PMC 1502536. PMID 16782814.
  22. ^ Yang, Ming; Chowdhury, Rasheduzzaman; Ge, Wei; Hamed, Refaat B.; McDonough, Michael A.; Claridge, Timothy D. W.; Kessler, Benedikt M.; Cockman, Matthew E.; Ratcliffe, Peter J. (1 April 2011). "Factor-inhibiting hypoxia-inducible factor (FIH) catalyses the post-translational hydroxylation of histidinyl residues within ankyrin repeat domains". FEBS Journal. 278 (7): 1086–1097. doi:10.1111/j.1742-4658.2011.08022.x. ISSN 1742-4658. PMC 3569879. PMID 21251231.
  23. ^ Langley, Gareth W.; Brinkø, Anne; Münzel, Martin; Walport, Louise J.; Schofield, Christopher J.; Hopkinson, Richard J. (25 November 2015). "Analysis of JmjC Demethylase-Catalyzed Demethylation Using Geometrically-Constrained Lysine Analogues". ACS Chemical Biology. 11 (3): 755–762. doi:10.1021/acschembio.5b00738. PMID 26555343. S2CID 19124771.
  24. ^ Walport, Louise J.; Hopkinson, Richard J.; Chowdhury, Rasheduzzaman; Schiller, Rachel; Ge, Wei; Kawamura, Akane; Schofield, Christopher J. (23 June 2016). "Arginine demethylation is catalysed by a subset of JmjC histone lysine demethylases". Nature Communications. 7: 11974. Bibcode:2016NatCo...711974W. doi:10.1038/ncomms11974. PMC 4931022. PMID 27337104.
  25. ^ Ng, Stanley S.; Kavanagh, Kathryn L.; McDonough, Michael A.; Butler, Danica; Pilka, Ewa S.; Lienard, Benoit M. R.; Bray, James E.; Savitsky, Pavel; Gileadi, Opher (5 July 2007). "Crystal structures of histone demethylase JMJD2A reveal basis for substrate specificity". Nature. 448 (7149): 87–91. Bibcode:2007Natur.448...87N. doi:10.1038/nature05971. ISSN 0028-0836. PMID 17589501. S2CID 4331492.
  26. ^ Kawamura, Akane; Loenarz, Christoph; Schofield, Christopher J. (1 September 2011). "Mutations to metabolic enzymes in cancer herald a need to unify genetics and biochemistry". Cell Cycle. 10 (17): 2819–2820. doi:10.4161/cc.10.17.16745. ISSN 1538-4101. PMID 21857150.
  27. ^ Rotili, Dante; Tomassi, Stefano; Conte, Mariarosaria; Benedetti, Rosaria; Tortorici, Marcello; Ciossani, Giuseppe; Valente, Sergio; Marrocco, Biagina; Labella, Donatella (19 December 2013). "Pan-Histone Demethylase Inhibitors Simultaneously Targeting Jumonji C and Lysine-Specific Demethylases Display High Anticancer Activities". Journal of Medicinal Chemistry. 57 (1): 42–55. doi:10.1021/jm4012802. hdl:11573/542432. PMID 24325601.
  28. ^ Kruidenier, Laurens; Chung, Chun-wa; Cheng, Zhongjun; Liddle, John; Che, KaHing; Joberty, Gerard; Bantscheff, Marcus; Bountra, Chas; Bridges, Angela (16 August 2012). "A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response". Nature. 488 (7411): 404–408. Bibcode:2012Natur.488..404K. doi:10.1038/nature11262. ISSN 0028-0836. PMC 4691848. PMID 22842901.
  29. ^ Lercher, Lukas; McDonough, Michael A.; El-Sagheer, Afaf H.; Thalhammer, Armin; Kriaucionis, Skirmantas; Brown, Tom; Schofield, Christopher J. (23 January 2014). "Structural insights into how 5-hydroxymethylation influences transcription factor binding". Chemical Communications. 50 (15): 1794–1796. doi:10.1039/C3CC48151D. ISSN 1364-548X. PMID 24287551. S2CID 6489226.
  30. ^ Church, Chris; Lee, Sheena; Bagg, Eleanor A. L.; McTaggart, James S.; Deacon, Robert; Gerken, Thomas; Lee, Angela; Moir, Lee; Mecinović, Jasmin (14 August 2009). "A Mouse Model for the Metabolic Effects of the Human Fat Mass and Obesity Associated FTO Gene". PLOS Genet. 5 (8): e1000599. doi:10.1371/journal.pgen.1000599. ISSN 1553-7404. PMC 2719869. PMID 19680540.
  31. ^ Aik, WeiShen; Demetriades, Marina; Hamdan, Muhammad K. K.; Bagg, Eleanor. A. L.; Yeoh, Kar Kheng; Lejeune, Clarisse; Zhang, Zhihong; McDonough, Michael A.; Schofield, Christopher J. (23 April 2013). "Structural Basis for Inhibition of the Fat Mass and Obesity Associated Protein (FTO)". Journal of Medicinal Chemistry. 56 (9): 3680–3688. doi:10.1021/jm400193d. PMID 23547775.
  32. ^ Gerken, Thomas; Girard, Christophe A.; Tung, Yi-Chun Loraine; Webby, Celia J.; Saudek, Vladimir; Hewitson, Kirsty S.; Yeo, Giles S. H.; McDonough, Michael A.; Cunliffe, Sharon (30 November 2007). "The Obesity-Associated FTO Gene Encodes a 2-Oxoglutarate-Dependent Nucleic Acid Demethylase". Science. 318 (5855): 1469–1472. Bibcode:2007Sci...318.1469G. doi:10.1126/science.1151710. ISSN 0036-8075. PMC 2668859. PMID 17991826.
  33. ^ Church, Chris; Lee, Sheena; Bagg, Eleanor A. L.; McTaggart, James S.; Deacon, Robert; Gerken, Thomas; Lee, Angela; Moir, Lee; Mecinović, Jasmin (14 August 2009). "A Mouse Model for the Metabolic Effects of the Human Fat Mass and Obesity Associated FTO Gene". PLOS Genet. 5 (8): e1000599. doi:10.1371/journal.pgen.1000599. ISSN 1553-7404. PMC 2719869. PMID 19680540.
  34. ^ Mantri, Monica; Krojer, Tobias; Bagg, Eleanor A.; Webby, Celia J.; Butler, Danica S.; Kochan, Grazyna; Kavanagh, Kathryn L.; Oppermann, Udo; McDonough, Michael A. (13 August 2010). "Crystal Structure of the 2-Oxoglutarate- and Fe(II)-Dependent Lysyl Hydroxylase JMJD6". Journal of Molecular Biology. 401 (2): 211–222. doi:10.1016/j.jmb.2010.05.054. PMID 20685276.
  35. ^ Clifton, Ian J.; McDonough, Michael A.; Ehrismann, Dominic; Kershaw, Nadia J.; Granatino, Nicolas; Schofield, Christopher J. (1 April 2006). "Structural studies on 2-oxoglutarate oxygenases and related double-stranded β-helix fold proteins". Journal of Inorganic Biochemistry. High-valent iron intermediates in biologyHigh-valent iron intermediates in biology. 100 (4): 644–669. doi:10.1016/j.jinorgbio.2006.01.024. PMID 16513174.
  36. ^ Welford, Richard W.D.; Kirkpatrick, Joanna M.; McNeill, Luke A.; Puri, Munish; Oldham, Neil J.; Schofield, Christopher J. (5 December 2005). "Corrigendum to "Incorporation of oxygen into the succinate co-product of iron(II) and 2-oxoglutarate dependent oxygenases from bacteria, plants and humans (FEBS 29930)" [FEBS Lett. 579 (2005) 5170–5174]". FEBS Letters. 579 (29): 6688. doi:10.1016/j.febslet.2005.11.001. hdl:10536/DRO/DU:30095401. ISSN 1873-3468.
  37. ^ Loenarz, Christoph; Mecinović, Jasmin; Chowdhury, Rasheduzzaman; McNeill, LukeA.; Flashman, Emily; Schofield, ChristopherJ. (23 February 2009). "Evidence for a Stereoelectronic Effect in Human Oxygen Sensing". Angewandte Chemie International Edition. 48 (10): 1784–1787. doi:10.1002/anie.200805427. ISSN 1521-3773. PMID 19180614.
  38. ^ Astuti, Dewi; Ricketts, Christopher J.; Chowdhury, Rasheduzzaman; McDonough, Michael A.; Gentle, Dean; Kirby, Gail; Schlisio, Susanne; Kenchappa, Rajappa S.; Carter, Bruce D. (1 February 2011). "Mutation analysis of HIF prolyl hydroxylases (PHD/EGLN) in individuals with features of phaeochromocytoma and renal cell carcinoma susceptibility". Endocrine-Related Cancer. 18 (1): 73–83. doi:10.1677/ERC-10-0113. ISSN 1351-0088. PMC 3006001. PMID 20959442.
  39. ^ Rose, Nathan R.; McDonough, Michael A.; King, Oliver N. F.; Kawamura, Akane; Schofield, Christopher J. (14 July 2011). "Inhibition of 2-oxoglutarate dependent oxygenases". Chemical Society Reviews. 40 (8): 4364–97. doi:10.1039/C0CS00203H. ISSN 1460-4744. PMID 21390379.
  40. ^ Aik, WeiShen; Scotti, John S.; Choi, Hwanho; Gong, Lingzhi; Demetriades, Marina; Schofield, Christopher J.; McDonough, Michael A. (1 April 2014). "Structure of human RNA N6-methyladenine demethylase ALKBH5 provides insights into its mechanisms of nucleic acid recognition and demethylation". Nucleic Acids Research. 42 (7): 4741–4754. doi:10.1093/nar/gku085. ISSN 0305-1048. PMC 3985658. PMID 24489119.
  41. ^ Mackeen, Mukram M.; Kramer, Holger B.; Chang, Kai-Hsuan; Coleman, Matthew L.; Hopkinson, Richard J.; Schofield, Christopher J.; Kessler, Benedikt M. (21 July 2010). "Small-Molecule-Based Inhibition of Histone Demethylation in Cells Assessed by Quantitative Mass Spectrometry". Journal of Proteome Research. 9 (8): 4082–4092. doi:10.1021/pr100269b. PMC 4681095. PMID 20583823.
  42. ^ Clifton, Ian J.; Hsueh, Li-Ching; Baldwin, Jack E.; Harlos, Karl; Schofield, Christopher J. (15 December 2001). "Structure of proline 3-hydroxylase". European Journal of Biochemistry. 268 (24): 6625–6636. doi:10.1046/j.0014-2956.2001.02617.x. ISSN 1432-1033. PMID 11737217.
  43. ^ Mbenza NM, Vadakkedath PG, McGillivray DJ, Leung IK (December 2017). "NMR studies of the non-haem Fe(II) and 2-oxoglutarate-dependent oxygenases". J. Inorg. Biochem. 177: 384–394. doi:10.1016/j.jinorgbio.2017.08.032. PMID 28893416.
  44. ^ Khan A, Leśniak RK, Brem J, Rydzik AM, Choi H, Leung IK, McDonough MA, Schofield CJ, Claridge TD (February 2016). "Development and application of ligand-based NMR screening assays for γ-butyrobetaine hydroxylase". Med. Chem. Commun. 7 (5): 873–880. doi:10.1039/C6MD00004E. hdl:2292/30083.
  45. ^ Leung IK, Demetriades M, Hardy AP, Lejeune C, Smart TJ, Szöllössi A, Kawamura A, Schofield CJ, Claridge TD (January 2013). "Reporter ligand NMR screening method for 2-oxoglutarate oxygenase inhibitors". J. Med. Chem. 56 (2): 547–555. doi:10.1021/jm301583m. PMC 4673903. PMID 23234607.
  46. ^ Leung IK, Flashman E, Yeoh KK, Schofield CJ, Claridge TD (January 2010). "Using NMR solvent water relaxation to investigate metalloenzyme-ligand binding interactions". J. Med. Chem. 53 (2): 867–875. doi:10.1021/jm901537q. PMID 20025281.
  47. ^ Rydzik AM, Leung IK, Thalhammer A, Kochan GT, Claridge TD, Schofield CJ (February 2014). "Fluoromethylated derivatives of carnitine biosynthesis intermediates - synthesis and applications". Chem. Commun. 50 (10): 1175–1177. doi:10.1039/c3cc47581f. PMID 24317009.
  48. ^ Mecinović, Jasmin; Chowdhury, Rasheduzzaman; Flashman, Emily; Schofield, Christopher J. (15 October 2009). "Use of mass spectrometry to probe the nucleophilicity of cysteinyl residues of prolyl hydroxylase domain 2". Analytical Biochemistry. 393 (2): 215–221. doi:10.1016/j.ab.2009.06.029. PMID 19563769.
  49. ^ Tan, SuatCheng; Carr, CarolynA.; Yeoh, KarKheng; Schofield, ChristopherJ.; Davies, KayE.; Clarke, Kieran (1 April 2012). "Identification of valid housekeeping genes for quantitative RT-PCR analysis of cardiosphere-derived cells preconditioned under hypoxia or with prolyl-4-hydroxylase inhibitors". Molecular Biology Reports. 39 (4): 4857–4867. doi:10.1007/s11033-011-1281-5. ISSN 0301-4851. PMC 3294216. PMID 22065248.
  50. ^ Rydzik AM, Leung IK, Kochan GT, Thalhammer A, Oppermann U, Claridge TD, Schofield CJ (July 2012). "Development and application of a fluoride-detection-based fluorescence assay for γ-butyrobetaine hydroxylase". ChemBioChem. 13 (11): 1559–1563. doi:10.1002/cbic.201200256. PMID 22730246. S2CID 13956474.
  51. ^ Flashman, Emily; Bagg, Eleanor A. L.; Chowdhury, Rasheduzzaman; Mecinović, Jasmin; Loenarz, Christoph; McDonough, Michael A.; Hewitson, Kirsty S.; Schofield, Christopher J. (15 February 2008). "Kinetic Rationale for Selectivity toward N- and C-terminal Oxygen-dependent Degradation Domain Substrates Mediated by a Loop Region of Hypoxia-Inducible Factor Prolyl Hydroxylases". Journal of Biological Chemistry. 283 (7): 3808–3815. doi:10.1074/jbc.M707411200. ISSN 0021-9258. PMID 18063574.
  52. ^ Demetriades M, Leung IK, Chowdhury R, Chan MC, McDonough MA, Yeoh KK, Tian YM, Claridge TD, Ratcliffe PJ, Woon EC, Schofield CJ (July 2012). "Dynamic combinatorial chemistry employing boronic acids/boronate esters leads to potent oxygenase inhibitors". Angew. Chem. Int. Ed. 51 (27): 6672–6675. doi:10.1002/anie.201202000. PMID 22639232.
  53. ^ Leung IK, Brown T Jr, Schofield CJ, Claridge TD (March 2011). "An approach to enzyme inhibition employing reversible boronate ester formation". Med. Chem. Commun. 2 (5): 390–395. doi:10.1039/C1MD00011J.
  54. ^ Chan, Mun Chiang; Atasoylu, Onur; Hodson, Emma; Tumber, Anthony; Leung, Ivanhoe K. H.; Chowdhury, Rasheduzzaman; Gómez-Pérez, Verónica; Demetriades, Marina; Rydzik, Anna M. (6 July 2015). "Potent and Selective Triazole-Based Inhibitors of the Hypoxia-Inducible Factor Prolyl-Hydroxylases with Activity in the Murine Brain". PLOS ONE. 10 (7): e0132004. Bibcode:2015PLoSO..1032004C. doi:10.1371/journal.pone.0132004. ISSN 1932-6203. PMC 4492579. PMID 26147748.
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