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The Abell Group

 

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 two fold, 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 Professor Andrew Munro and Professor David Leys at the University of Manchester.

X-ray crystal structures of inhibitors of CYP121 from Mycobacterium tuberculosis:

Related Publications 

Fragment Profiling Approach to Inhibitors of the Orphan M. tuberculosis P450 CYP144A1
ME Kavanagh, J Chenge, A Zoufir, KJ McLean, AG Coyne, A Bender, AW Munro, C Abell – Biochemistry (2017) 56, 1559
Substrate Fragmentation for the Design of M. tuberculosis CYP121 Inhibitors.
ME Kavanagh, JL Gray, SH Gilbert, AG Coyne, KJ McLean, HJ Davis, AW Munro, C Abell – ChemMedChem (2016) 11, 1924
Corrigendum: Substrate Fragmentation for the Design of M. tuberculosis CYP121 Inhibitors.
ME Kavanagh, JL Gray, SH Gilbert, AG Coyne, KJ McLean, HJ Davis, AW Munro, C Abell – ChemMedChem (2017) 12, 194
Fragment-Based Approaches to the Development of Mycobacterium tuberculosis CYP121 Inhibitors
ME Kavanagh, AG Coyne, KJ McLean, GG James, CW Levy, LB Marino, LPS de Carvalho, DSH Chan, SA Hudson, S Surade, D Leys, AW Munro, C Abell – J Med Chem (2016) 59, 3272
Overcoming the Limitations of Fragment Merging: Rescuing a Strained Merged Fragment Series Targeting Mycobacterium tuberculosis CYP121
SA Hudson, S Surade, AG Coyne, KJ McLean, D Leys, AW Munro, C Abell – ChemMedChem (2013) 8, 1451
Application of Fragment Screening and Merging to the Discovery of Inhibitors of the Mycobacterium tuberculosis Cytochrome P450 CYP121
SA Hudson, KJ McLean, S Surade, Y-Q Yang, D Leys, A Ciulli, AW Munro, C Abell – Angew Chem Int Ed Engl (2012) 51, 9311