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Cytochrome P450s

We are using fragment-based approaches to understand of the role of cytochrome P450 enzymes (CYPs) from Mycobacterium tuberculosis. CYPs are mon-oxygenases responsible for a range of oxidative modifications. M. tuberculosis has a relatively high number of CYPs, some of which are essential, and some of which are of unknown function. Our interests are therefore twofold, to develop isoform specific inhibitors as chemical tools (and potential therapeutic leads) and also to try and identify the substrates of the orphan CYPs. This research is a collaboration with Prof Andrew Munro, Prof David Leys and Dr Kirsty Mclean, University of Manchester.

CYP121 Fragments X-ray of novel CYP121 inhibitor
X-ray crystal structure of fragments which bind to CYP121
[Angew. Chem. Int. Ed. 2012]
X-ray crystal structure of novel CYP121 inhibitor discovered through fragment elaboration strategies
[ChemMedChem 2013] [J Med Chem 2016]

Related Publications

   Fragment-Based Approaches to the Development of Mycobacterium tuberculosis CYP121 Inhibitors
ME Kavanagh, AG Coyne, KJ McLean, GG James, CW Levy, LB Marino, LP de Carvalho, DS Chan, SA Hudson, S Surade, D Leys, AW Munro, C Abell
J Med Chem, (2016), 59, 3272-3302
DOI: 10.1021/acs.jmedchem.6b00007
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   Biofragments: an approach towards predicting protein function using biologically related fragments and its application to mycobacterium tuberculosis CYP126
S A Hudson, E H Mashalidis, A Bender, K J McLean, A W Munro, C Abell
ChemBioChem, 2014, 5, 549-555
DOI: 10.1002/cbic.201300697
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   Overcoming the limitations of fragment merging: rescuing a strained merged fragment series targeting Mycobacterium tuberculosis CYP121
S A Hudson, S Surade, A G Coyne, K J McLean, D Leys, A W Munro, C Abell
ChemMedChem, 2013, 8, 1451-1456
DOI: 10.1002/cmdc.201300219
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   Application of fragment screening and merging to the discovery of inhibitors of the Mycobacterium tuberculosis cytochrome P450 CYP121
S A Hudson, K J McLean, S Surade, Y Q Yang, D Leys, A Ciulli, A W Munro, C Abell
Angew. Chem. Int. Ed. 2012, 51 , 9311-9316
DOI: 10.1002/anie.201202544
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   Mycobacterium tuberculosis cytochrome P450 enzymes: a cohort of novel TB drug targets
S A Hudson, K J McLean, A W Munro, C Abell
Biochem. Soc. Trans. 2012, 40, 573-579
DOI: 10.1042/BST20120062
Read article

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