Shane R Wilkinson

Summary

Affiliation: Queen Mary
Country: UK

Publications

  1. ncbi A mechanism for cross-resistance to nifurtimox and benznidazole in trypanosomes
    Shane R Wilkinson
    School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, United Kingdom
    Proc Natl Acad Sci U S A 105:5022-7. 2008
  2. ncbi Trypanocidal drugs: mechanisms, resistance and new targets
    Shane R Wilkinson
    Queen Mary Pre Clinical Drug Discovery Group, School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, UK
    Expert Rev Mol Med 11:e31. 2009
  3. ncbi Trypanocidal activity of nitroaromatic prodrugs: current treatments and future perspectives
    Shane R Wilkinson
    Queen Mary Pre Clinical Drug Discovery Group, School of Biological and Chemical Sciences, Queen Mary University of London, UK
    Curr Top Med Chem 11:2072-84. 2011
  4. ncbi Nifurtimox activation by trypanosomal type I nitroreductases generates cytotoxic nitrile metabolites
    Belinda S Hall
    School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, United Kingdom
    J Biol Chem 286:13088-95. 2011
  5. ncbi Trypanocidal activity of aziridinyl nitrobenzamide prodrugs
    Chris Bot
    Queen Mary Pre Clinical Drug Discovery Group, School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, United Kingdom
    Antimicrob Agents Chemother 54:4246-52. 2010
  6. ncbi Exploiting the drug-activating properties of a novel trypanosomal nitroreductase
    Belinda S Hall
    Queen Mary Pre Clinical Drug Discovery Group, School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, United Kingdom
    Antimicrob Agents Chemother 54:1193-9. 2010
  7. ncbi Activation of benznidazole by trypanosomal type I nitroreductases results in glyoxal formation
    Belinda S Hall
    Queen Mary Pre Clinical Drug Discovery Group, School of Biological and Chemical Sciences, Queen Mary University of London, London, United Kingdom
    Antimicrob Agents Chemother 56:115-23. 2012
  8. ncbi Peroxiredoxins play a major role in protecting Trypanosoma cruzi against macrophage- and endogenously-derived peroxynitrite
    Lucia Piacenza
    Departamento de Bioquímica and Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay
    Biochem J 410:359-68. 2008
  9. ncbi Insights into the redox biology of Trypanosoma cruzi: Trypanothione metabolism and oxidant detoxification
    Florencia Irigoín
    Departmento de Histología y Embriología, Facultad de Medicina, Universidad de la Republica, Uruguay
    Free Radic Biol Med 45:733-42. 2008
  10. ncbi Validation of spermidine synthase as a drug target in African trypanosomes
    Martin C Taylor
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
    Biochem J 409:563-9. 2008

Collaborators

Detail Information

Publications20

  1. ncbi A mechanism for cross-resistance to nifurtimox and benznidazole in trypanosomes
    Shane R Wilkinson
    School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, United Kingdom
    Proc Natl Acad Sci U S A 105:5022-7. 2008
    ..This potential for drug resistance by a simple mechanism has important implications, because nifurtimox is currently undergoing phase III clinical trials against African trypanosomiasis...
  2. ncbi Trypanocidal drugs: mechanisms, resistance and new targets
    Shane R Wilkinson
    Queen Mary Pre Clinical Drug Discovery Group, School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, UK
    Expert Rev Mol Med 11:e31. 2009
    ....
  3. ncbi Trypanocidal activity of nitroaromatic prodrugs: current treatments and future perspectives
    Shane R Wilkinson
    Queen Mary Pre Clinical Drug Discovery Group, School of Biological and Chemical Sciences, Queen Mary University of London, UK
    Curr Top Med Chem 11:2072-84. 2011
    ..This approach has led to the identification of two new classes of anti-trypanosomal agents, nitrobenzylphosphoramide mustards and aziridinyl nitrobenzamides, and promises to yield new, safer, more effective drugs...
  4. ncbi Nifurtimox activation by trypanosomal type I nitroreductases generates cytotoxic nitrile metabolites
    Belinda S Hall
    School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, United Kingdom
    J Biol Chem 286:13088-95. 2011
    ..These experiments indicate that the basis for the selectivity of nifurtimox against T. brucei lies in the expression of a parasite-encoded type I nitroreductase...
  5. ncbi Trypanocidal activity of aziridinyl nitrobenzamide prodrugs
    Chris Bot
    Queen Mary Pre Clinical Drug Discovery Group, School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, United Kingdom
    Antimicrob Agents Chemother 54:4246-52. 2010
    ..We conclude that members of the aziridinyl nitrobenzamide class of nitroheterocycles provide new lead structures that have the potential to treat trypanosomal infections...
  6. ncbi Exploiting the drug-activating properties of a novel trypanosomal nitroreductase
    Belinda S Hall
    Queen Mary Pre Clinical Drug Discovery Group, School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, United Kingdom
    Antimicrob Agents Chemother 54:1193-9. 2010
    ..We conclude that halogenated nitrobenzylphosphoramide mustards represent a novel class of antitrypanosomal agents, and their efficacy validates the strategy of specifically targeting NTR activity to develop new therapeutics...
  7. ncbi Activation of benznidazole by trypanosomal type I nitroreductases results in glyoxal formation
    Belinda S Hall
    Queen Mary Pre Clinical Drug Discovery Group, School of Biological and Chemical Sciences, Queen Mary University of London, London, United Kingdom
    Antimicrob Agents Chemother 56:115-23. 2012
    ....
  8. ncbi Peroxiredoxins play a major role in protecting Trypanosoma cruzi against macrophage- and endogenously-derived peroxynitrite
    Lucia Piacenza
    Departamento de Bioquímica and Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay
    Biochem J 410:359-68. 2008
    ..Together with recent reports of up-regulation of antioxidant enzymes during metacyclogenesis, our results identify components of the antioxidant enzyme network of T. cruzi as virulence factors of emerging importance...
  9. ncbi Insights into the redox biology of Trypanosoma cruzi: Trypanothione metabolism and oxidant detoxification
    Florencia Irigoín
    Departmento de Histología y Embriología, Facultad de Medicina, Universidad de la Republica, Uruguay
    Free Radic Biol Med 45:733-42. 2008
    ..Together, the evidence suggests a central role of the trypanothione-dependent antioxidant systems in the infection process...
  10. ncbi Validation of spermidine synthase as a drug target in African trypanosomes
    Martin C Taylor
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
    Biochem J 409:563-9. 2008
    ..brucei cannot scavenge sufficient spermidine from their environment to meet growth requirements...
  11. ncbi The terminal step in vitamin C biosynthesis in Trypanosoma cruzi is mediated by a FMN-dependent galactonolactone oxidase
    Flora J Logan
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Biochem J 407:419-26. 2007
    ..The conserved lysine residue within this motif (Lys-450) is not required for cofactor binding, but its replacement by glycine renders the protein completely inactive...
  12. ncbi TcGPXII, a glutathione-dependent Trypanosoma cruzi peroxidase with substrate specificity restricted to fatty acid and phospholipid hydroperoxides, is localized to the endoplasmic reticulum
    Shane R Wilkinson
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Biochem J 364:787-94. 2002
    ..cruzi oxidative defence system by protecting newly synthesized lipids from peroxidation...
  13. ncbi Trypanosoma cruzi expresses a plant-like ascorbate-dependent hemoperoxidase localized to the endoplasmic reticulum
    Shane R Wilkinson
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
    Proc Natl Acad Sci U S A 99:13453-8. 2002
    ..These findings identify an arm of the oxidative defense system of this medically important parasite. The absence of this redox pathway in the human host may be therapeutically exploitable...
  14. ncbi The role of glutathione peroxidases in trypanosomatids
    Shane R Wilkinson
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
    Biol Chem 384:517-25. 2003
    ....
  15. ncbi The amino terminal domain of a novel WD repeat protein from Trypanosoma cruzi contains a non-canonical mitochondrial targeting signal
    Elizabeth V Bromley
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Int J Parasitol 34:63-71. 2004
    ..Interestingly this region lacks a typical amino terminal presequence suggesting that mitochondrial import is mediated by an alternative targeting signal...
  16. ncbi Functional mapping of a trypanosome centromere by chromosome fragmentation identifies a 16-kb GC-rich transcriptional "strand-switch" domain as a major feature
    Samson O Obado
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom
    Genome Res 15:36-43. 2005
    ..This unusual type of organization may represent a paradigm for centromeres in T. cruzi and other primitive eukaryotes...
  17. ncbi Vitamin C biosynthesis in trypanosomes: a role for the glycosome
    Shane R Wilkinson
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom
    Proc Natl Acad Sci U S A 102:11645-50. 2005
    ..It is implicit, therefore, that bloodstream-form trypanosomes also possess a capacity for ascorbate transport...
  18. ncbi Deletion of the Trypanosoma brucei superoxide dismutase gene sodb1 increases sensitivity to nifurtimox and benznidazole
    S Radhika Prathalingham
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom
    Antimicrob Agents Chemother 51:755-8. 2007
    ..Here, we identify a superoxide dismutase required to protect Trypanosoma brucei from drug-generated superoxide...
  19. ncbi Mitochondrial superoxide radicals mediate programmed cell death in Trypanosoma cruzi: cytoprotective action of mitochondrial iron superoxide dismutase overexpression
    Lucia Piacenza
    Departamento de Bioquimica, Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay
    Biochem J 403:323-34. 2007
    ....
  20. ncbi The Trypanosoma cruzi enzyme TcGPXI is a glycosomal peroxidase and can be linked to trypanothione reduction by glutathione or tryparedoxin
    Shane R Wilkinson
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom
    J Biol Chem 277:17062-71. 2002
    ..The ability of TcGPXI to use alternative electron donors may reflect their availability at the corresponding subcellular sites...