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A new approach for potential drug target discovery through in silico metabolic pathway analysis using Trypanosoma cruzi genome information
Alves-Ferreira, Marcelo; Guimarães, Ana Carolina Ramos; Capriles, Priscila Vanessa da Silva Zabala; Dardenne, Laurent E; Degrave, Wim M.
  • Alves-Ferreira, Marcelo; Instituto Oswaldo Cruz-Fiocruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro. BR
  • Guimarães, Ana Carolina Ramos; Instituto Oswaldo Cruz-Fiocruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro. BR
  • Capriles, Priscila Vanessa da Silva Zabala; Ministério da Ciência e Tecnologia. Laboratório Nacional de Computação Científica. Grupo de Modelagem Molecular de Sistemas Biológicos. Petrópolis. BR
  • Dardenne, Laurent E; Ministério da Ciência e Tecnologia. Laboratório Nacional de Computação Científica. Grupo de Modelagem Molecular de Sistemas Biológicos. Petrópolis. BR
  • Degrave, Wim M; Instituto Oswaldo Cruz-Fiocruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro. BR
Mem. Inst. Oswaldo Cruz ; 104(8): 1100-1110, Dec. 2009. ilus, tab
Article in English | LILACS | ID: lil-538169
ABSTRACT
The current drug options for the treatment of chronic Chagas disease have not been sufficient and high hopes have been placed on the use of genomic data from the human parasite Trypanosoma cruzi to identify new drug targets and develop appropriate treatments for both acute and chronic Chagas disease. However, the lack of a complete assembly of the genomic sequence and the presence of many predicted proteins with unknown or unsure functions has hampered our complete view of the parasite's metabolic pathways. Moreover, pinpointing new drug targets has proven to be more complex than anticipated and has revealed large holes in our understanding of metabolic pathways and their integrated regulation, not only for this parasite, but for many other similar pathogens. Using an in silicocomparative study on pathway annotation and searching for analogous and specific enzymes, we have been able to predict a considerable number of additional enzymatic functions in T. cruzi. Here we focus on the energetic pathways, such as glycolysis, the pentose phosphate shunt, the Krebs cycle and lipid metabolism. We point out many enzymes that are analogous to those of the human host, which could be potential new therapeutic targets.
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Full text: Available Index: LILACS (Americas) Main subject: Trypanocidal Agents / Trypanosoma cruzi / Genome, Protozoan / Metabolic Networks and Pathways / Drug Discovery Limits: Humans Language: English Journal: Mem. Inst. Oswaldo Cruz Journal subject: Tropical Medicine / Parasitology Year: 2009 Type: Article Affiliation country: Brazil Institution/Affiliation country: Instituto Oswaldo Cruz-Fiocruz/BR / Ministério da Ciência e Tecnologia/BR

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Full text: Available Index: LILACS (Americas) Main subject: Trypanocidal Agents / Trypanosoma cruzi / Genome, Protozoan / Metabolic Networks and Pathways / Drug Discovery Limits: Humans Language: English Journal: Mem. Inst. Oswaldo Cruz Journal subject: Tropical Medicine / Parasitology Year: 2009 Type: Article Affiliation country: Brazil Institution/Affiliation country: Instituto Oswaldo Cruz-Fiocruz/BR / Ministério da Ciência e Tecnologia/BR