Optimization of Inhibitors of Mycobacterium tuberculosis Pantothenate Synthetase Based on Group Efficiency Analysis
Hung, Alvin W
Silvestre, H Leonardo
George, Guillaume PC
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Hung, A. W., Silvestre, H. L., Web, S., George, G. P., Boland, J., Blundell, T., Ciulli, A., & et al. (2015). Optimization of Inhibitors of Mycobacterium tuberculosis Pantothenate Synthetase Based on Group Efficiency Analysis. ChemMedChem, 11 38-42. https://doi.org/10.1002/cmdc.201500414
Group efficiency analysis is used to systematically improve the potency of inhibitors of Mycobacterium tuberculosis pantothenate synthetase. Binding efficiencies were found to be distributed unevenly within a lead molecule derived using a fragment-based approach. Substitution of the less efficient parts of this molecule allowed systematic development of more potent compounds. This method of dissecting and analyzing different groups within a molecule offers a rational and general way of carrying out lead optimization.
Acknowledgements: This research was supported by the Bill & Melinda Gates Foundation[“Integrated Methods for TB Drug Development(IMTB)” Accelerator Grant], the UK Biotechnology and Biological Sciences Research Council (Grant BB/D006104/1), the Fundação para a Ciência e Tecnologia (PhD sponsorship to H.L.S.), and Homerton College (Junior Research Fellowship to A.C.).
External DOI: https://doi.org/10.1002/cmdc.201500414
This record's URL: https://www.repository.cam.ac.uk/handle/1810/251365
Creative Commons Attribution 4.0
Licence URL: http://creativecommons.org/licenses/by/4.0/