研究领域

Organic Chemistry

Our research is driven by a desire to apply chemical principles and techniques to understanding biology. A recent focus of our current work is contributing to a chemical understanding of genetics including how information can be transferred between generations without changes in the 'ATCG' DNA sequence (epigenetics). We have also worked closely with clinical researchers to uncover the mechanism by which humans sense and respond to changes in oxygen levels; This work is important for understanding how tumours grow and how animals adapt to limiting oxygen, e.g. on going to altitude. We apply the knowledge gained in our basic research to the design and synthesis of enzyme inhibitors for proof of principle' therapeutic use, in understanding biosynthetic and signaling pathways and in pioneering new methods for medicine. A variety of techniques are used in our research, including synthetic chemistry, enzyme purification and characterisation, cloning/mutagenesis, and biophysical techniques including X-ray crystallography, NMR and mass spectrometry. We intend that all of our projects involve interesting chemistry combined with biomedicinal applications and are of basic science interest.

近期论文

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Structural studies on human 2-oxoglutarate oxygenases McDonough MA, Loenarz C, Chowdhury R, Clifton IJ, Schofield CJ Current Opinion in Structural Biology, 2010, 20, 1-13. Crystal structure of the 2-oxoglutarate- and Fe(II)-dependent lysyl hydroxylase JMJD6 Mantri, M; Krojer, T; Bagg, EA, Webby, CJ, Butler, Danica S, Kochan G, Kavanagh, KL, Oppermann, U, McDonough, MA, Schofield CJ Journal of Molecular Biology 2010, 401, 211-222. Chemical basis for the selectivity of the von Hippel Lindau tumor suppressor pVHL for prolyl-hydroxylated HIF-1 alpha Illingworth, CJR; Loenarz, C; Schofield, CJ, Domene, C Biochemistry 2010, 49, 6936-6944. Structural basis for the interaction of Lactivicins with serine beta-lactamases Brown, T; Charlier, P; Herman, R, Schofield CJ, Sauvage, E Journal of Medicinal Chemistry 2010, 53, 5890-5894. Small-Molecule-Based Inhibition of Histone Demethylation in Cells Assessed by Quantitative Mass Spectrometry Mackeen, MM; Kramer, HB; Chang, KH, Coleman ML, Hopkinson RJ, Schofield CJ, Kessler BM Journal of Proteome Research 2010, 9, 4082-4092. A miniaturized screen for inhibitors of Jumonji histone demethylases Sakurai, M; Rose, NR; Schultz, L, Quinn AM, Jadhav, A, Ng, SS, Oppermann U, Schofield CJ, Simeonov A Molecular Biosystems 2010, 6, 357-364. Small-Molecule-Based Inhibition of Histone Demethylation in Cells Assessed by Quantitative Mass Spectrometry Mackeen, MM; Kramer, HB; Chang, KH, Coleman ML, Hopkinson RJ, Schofield CJ, Kessler BM Journal of Proteome Research 2010, 9, 4082-4092. Development of homogeneous luminescence assays for histone demethylase catalysis and binding Kawamura, A; Tumber, A; Rose, NR, King ONF, Daniel M, Oppermann U, Heightman T, Schofield CJ Analytical Biochemistry 2010, 404, 86-93. Fast and forceful refolding of stretched alpha-helical solenoid proteins Kim M, Abdi K, Lee G, Rabbi M, Lee W, Yang M, Schofield CJ, Bennett V, Marszalek PE Biophysical Journal 2010, 98, 3086-3092. Crystal structure of the PHF8 Jumonji domain, an N-epsilon-methyl lysine demethylase Yue WW, Hozjan V, Ge W, Loenarz C, Cooper CDO, Schofield CJ, Kavanagh KL, Oppermann U, McDonough MA FEBS Letters 2010, 584, 825-830. 2-Oxoglutarate oxygenases are inhibited by a range of transition metals Sekirnik R, Rose NR, Mecinovic J, Schofield CJ Metallomics 2010, 2, 397-399. Selective inhibitors of the JMJD2 histone demethylases: Combined nondenaturing mass spectrometric screening and crystallographic approaches Rose NR, Woon ECY, Kingham GL, King ONF, Mecinovic J, Clifton IJ, Ng SS, Talib-Hardy J, Oppermann U, McDonough MA, and Schofield CJ Journal of Medicinal Chemistry 2010, 53, 1810-1818. Therapeutic manipulation of the HIF hydroxylases, Nagel S, Talbot NP, Mecinovic J, Smith TG, Buchan AM, and Schofield CJ Antioxidants & Redox Signaling 2010, 12, 481-501. Crystal structures of an oligopeptide-binding protein from the biosynthetic pathway of the beta-lactamase inhibitor clavulanic acid Mackenzie AK, Valegard K, Iqbal A, Caines MEC, Kershaw NJ, Jensen SE, Schofield CJ, and Andersson I Journal of Molecular Biology 2010, 396, 332-344. Crystallographic and mass spectrometric analyses of a tandem GNAT protein from the clavulanic acid biosynthesis pathway Crystallographic and mass spectrometric analyses of a tandem GNAT protein from the clavulanic acid biosynthesis pathway Monitoring the activity of 2-oxoglutarate dependent histone demethylases by NMR Spectroscopy: Direct Observation of Formaldehyde Hopkinson RJ, Hamed RB, Rose NR, Claridge TDW, and Schofield CJ ChemBioChem 2010, 11, 506-510. Carboxymethylproline synthase catalysed syntheses of functionalised N-heterocycles Hamed RB, Mecinovic J, Ducho C, Claridge TDW, and Schofield CJ Chemical Communications 2010, 46, 1413-1415. Investigating the dependence of the hypoxia-inducible factor hydroxylases (factor inhibiting HIF and prolyl hydroxylase domain 2) on ascorbate and other reducing agents, Flashman E, Davies SL, Yeoh KK, and Schofield CJ Biochemical Journal 2010, 427, 135-142. PHF8, a gene associated with cleft lip/palate and mental retardation, encodes for an N-epsilon-dimethyl lysine demethylase Loenarz C, Ge W, Coleman ML, Rose NR, Cooper CDO, Klose RJ, Ratcliffe PJ, Schofield CJ Human Molecular Genetics 2010, 19, 217-222. Using NMR solvent water relaxation to investigate metalloenzyme-ligand binding interactions Leung IKH, Flashman E, Yeoh KK, Schofield CJ, Claridge TDW Journal of Medicinal Chemistry 2010 53, 867-875. Observations on the deprotection of pinanediol and pinacol boronate esters via fluorinated intermediates Inglis SR, Woon ECY, Thompson AL, Schofield CJ Journal of Organic Chemistry 2010, 75, 468-471.