Nature Communications (Feb 2021)
Fast acting allosteric phosphofructokinase inhibitors block trypanosome glycolysis and cure acute African trypanosomiasis in mice
- Iain W. McNae,
- James Kinkead,
- Divya Malik,
- Li-Hsuan Yen,
- Martin K. Walker,
- Chris Swain,
- Scott P. Webster,
- Nick Gray,
- Peter M. Fernandes,
- Elmarie Myburgh,
- Elizabeth A. Blackburn,
- Ryan Ritchie,
- Carol Austin,
- Martin A. Wear,
- Adrian J. Highton,
- Andrew J. Keats,
- Antonio Vong,
- Jacqueline Dornan,
- Jeremy C. Mottram,
- Paul A. M. Michels,
- Simon Pettit,
- Malcolm D. Walkinshaw
Affiliations
- Iain W. McNae
- Wellcome Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Michael Swann Building, Max Born Crescent
- James Kinkead
- Wellcome Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Michael Swann Building, Max Born Crescent
- Divya Malik
- Wellcome Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Michael Swann Building, Max Born Crescent
- Li-Hsuan Yen
- Wellcome Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Michael Swann Building, Max Born Crescent
- Martin K. Walker
- Selcia Ltd., Fyfield Business and Research Park, Fyfield Road, Ongar
- Chris Swain
- Cambridge MedChem Consulting
- Scott P. Webster
- Centre for Cardiovascular Science, College of Medicine and Veterinary Medicine, University of Edinburgh
- Nick Gray
- Wellcome Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Michael Swann Building, Max Born Crescent
- Peter M. Fernandes
- Wellcome Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Michael Swann Building, Max Born Crescent
- Elmarie Myburgh
- York Biomedical Research Institute, Hull York Medical School, University of York
- Elizabeth A. Blackburn
- Wellcome Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Michael Swann Building, Max Born Crescent
- Ryan Ritchie
- Institute of Infection Immunity and Inflammation, College of Medical Veterinary Life-Sciences, University of Glasgow
- Carol Austin
- Selcia Ltd., Fyfield Business and Research Park, Fyfield Road, Ongar
- Martin A. Wear
- Wellcome Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Michael Swann Building, Max Born Crescent
- Adrian J. Highton
- Selcia Ltd., Fyfield Business and Research Park, Fyfield Road, Ongar
- Andrew J. Keats
- Selcia Ltd., Fyfield Business and Research Park, Fyfield Road, Ongar
- Antonio Vong
- Selcia Ltd., Fyfield Business and Research Park, Fyfield Road, Ongar
- Jacqueline Dornan
- Wellcome Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Michael Swann Building, Max Born Crescent
- Jeremy C. Mottram
- York Biomedical Research Institute, Department of Biology, University of York
- Paul A. M. Michels
- Wellcome Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Michael Swann Building, Max Born Crescent
- Simon Pettit
- Selcia Ltd., Fyfield Business and Research Park, Fyfield Road, Ongar
- Malcolm D. Walkinshaw
- Wellcome Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Michael Swann Building, Max Born Crescent
- DOI
- https://doi.org/10.1038/s41467-021-21273-6
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 10
Abstract
Glycolytic enzymes are challenging drug targets due to their highly conserved active sites and phosphorylated substrates. Here, the authors identify fast acting allosteric inhibitors of Trypanosoma brucei phosphofructokinase that block trypanosome glycolysis and provide cure evidence in murine model.
