Trypanosoma cruzi chemical proteomics using immobilized benznidazole.

Abstract

Benznidazole (Bzn) is a nitroimidazole drug currently used as first line treatment against Chagas disease, a neglected tropical disease caused by the flagellated protozoan Trypanosoma cruzi. Although the drug has been used since the late 1960s, its mechanism of action is not fully understood. In an attempt to study Bzn mode of action, a structurally modified derivative of the drug was synthesized and immobilized into a solid matrix. This allowed enrichment of T. cruzi proteins capable of binding immobilized Bzn, which were subsequently analysed by mass spectrometry. The proteins identified as specific non-covalent Bzn interactors were a homologue of the bacterial YjeF proteins, a Sec23A orthologue and the aldo-ketoreductase family member TcAKR. TcAKR is closely related to other enzymes previously associated with Bzn reductive activation such as NTRI and TcOYE. Thus, our untargeted search for Bzn binding partners allowed us to encounter proteins that could be related to drug reductive activation and/or resistance mechanisms.

• Authors: Andrea Trochine, Guzmán Alvarez, Sandra Corre, Paula Faral-Tello, Rosario Durán, Carlos I Batthyany, Hugo Cerecetto, Mercedes González, Carlos Robello
• Journal: Experimental parasitology (Exp Parasitol) Vol. 140 Pg. 33-8 (May 2014) ISSN: 1090-2449 [Electronic] United States
• PMID: 24632192 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Nitroimidazoles
• Protozoan Proteins
• Trypanocidal Agents
• Tubulin
• Sepharose
• Aldo-Keto Reductases
• Aldehyde Reductase
• benzonidazole

Topics

• Aldehyde Reductase (metabolism)
• Aldo-Keto Reductases
• Chromatography, Affinity
• Electrophoresis, Polyacrylamide Gel
• Microspheres
• Nitroimidazoles (chemical synthesis, metabolism)
• Proteomics
• Protozoan Proteins (chemistry, metabolism)
• Sepharose (metabolism)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• Trypanocidal Agents (metabolism)
• Trypanosoma cruzi (enzymology, metabolism)
• Tubulin (chemistry, metabolism)