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The Abell Group

 

We have a long term interest in the enzymology of Coenzyme A, both the pathway up to pantothenate (vitamin B5) (present in plants, microorganisms and fungi) and the pathway from pantothenate to Coenzyme A (present in all cells) [Nat. Prod. Rep. 2004]. We have a specific interest in targeting the coenzyme A pathway enzymes (CoaBC, CoaD, CoaE) from Mycobacterium tuberculosis.

We use a range of biophysical techniques including thermal shift, NMR spectroscopy, ITC and X-ray crystallography to identify fragments that bind to these enzymes. These fragments act as starting points for elaboration to potent enzyme inhibitors. Our research in this area is in collaboration with Professor Tom Blundell (Biochemistry), Professor Val Mizrahi (University of Cape Town), Dr Clifton Barry III, Dr Helena Boshoff (NIH Bethesda, USA) and Dr Christina Spry (Australian National University).

Related Publications 

Optimization of Inhibitors of Mycobacterium tuberculosis Pantothenate Synthetase Based on Group Efficiency Analysis.
AW Hung, HL Silvestre, S Wen, GPC George, J Boland, TL Blundell, A Ciulli, C Abell – ChemMedChem (2016) 11, 38
Integrated biophysical approach to fragment screening and validation for fragment-based lead discovery
HL Silvestre, TL Blundell, C Abell, A Ciulli – Proceedings of the National Academy of Sciences of the United States of America (2013) 110, 12984
Optimization of the interligand Overhauser effect for fragment linking: application to inhibitor discovery against Mycobacterium tuberculosis pantothenate synthetase.
P Sledz, HL Silvestre, AW Hung, A Ciulli, TL Blundell, C Abell – Journal of the American Chemical Society (2010) 132, 4544
Application of fragment growing and fragment linking to the discovery of inhibitors of Mycobacterium tuberculosis pantothenate synthetase.
AW Hung, HL Silvestre, S Wen, A Ciulli, TL Blundell, C Abell – Angew Chem Int Ed Engl (2009) 48, 8452