Christopher J. Schofield
British chemist
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
^ a b "Christopher Schofield" . University of Oxford. Retrieved 24 July 2023 .
^ a b "Home – Schofield Group" . University of Oxford. Retrieved 8 August 2016 .
^ a b "Professor Chris Schofield FRS | Hertford College" . University of Oxford. Retrieved 8 August 2016 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ "ReOx Ltd - Oxford Spin-out to Develop New Drug Therapies" . Retrieved 8 August 2016 .
^ "SELECTBIO – Epigenetics Speaker Biography" . SELECTBIO . Retrieved 8 August 2016 .
^ a b "Christopher Schofield" . royalsociety.org. Retrieved 8 August 2016 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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. Bibcode :2005FEBSL.579.6688W . doi :10.1016/j.febslet.2005.11.001 . hdl :10536/DRO/DU:30095401 . ISSN 1873-3468 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ Thinnes, C. C.; Tumber, A.; Yapp, C.; Scozzafava, G.; Yeh, T.; Chan, M. C.; Tran, T. A.; Hsu, K.; Tarhonskaya, H. (8 October 2015). "Betti reaction enables efficient synthesis of 8-hydroxyquinoline inhibitors of 2-oxoglutarate oxygenases". Chemical Communications . 51 (84): 15458– 15461. doi :10.1039/C5CC06095H . ISSN 1364-548X . PMID 26345662 .
^ van Berkel, Sander S.; Nettleship, Joanne E.; Leung, Ivanhoe K. H.; Brem, Jürgen; Choi, Hwanho; Stuart, David I.; Claridge, Timothy D. W.; McDonough, Michael A.; Owens, Raymond J. (15 August 2013). "Binding of (5 S )-Penicilloic Acid to Penicillin Binding Protein 3". ACS Chemical Biology . 8 (10): 2112– 2116. doi :10.1021/cb400200h . PMID 23899657 .
^ MacKenzie, Alasdair K.; Kershaw, Nadia J.; Hernandez, Helena; Robinson, Carol V.; Schofield, Christopher J.; Andersson, Inger (19 January 2007). "Clavulanic Acid Dehydrogenase: Structural and Biochemical Analysis of the Final Step in the Biosynthesis of the β-Lactamase Inhibitor Clavulanic Acid † , ‡". Biochemistry . 46 (6): 1523– 1533. doi :10.1021/bi061978x . PMID 17279617 .
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^ Council, Biotechnology and Biological Sciences Research. "Research Advisory Panel – BBSRC" . bbsrc.ac.uk . Retrieved 25 February 2017 .
^ "Jeremy Knowles Award 2011 Winner" . rsc.org. Retrieved 25 February 2017 .
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