Format

Send to

Choose Destination
Exp Parasitol. 2014 May;140:33-8. doi: 10.1016/j.exppara.2014.03.013. Epub 2014 Mar 13.

Trypanosoma cruzi chemical proteomics using immobilized benznidazole.

Author information

1
Unidad de Biología Molecular, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo 11400, Uruguay. Electronic address: atrochine@gmail.com.
2
Grupo de Química Medicinal, Laboratorio de Química Orgánica, Facultad de Ciencias-Facultad de Química, Universidad de la República, Iguá 4225, Montevideo 11400, Uruguay. Electronic address: guzmanalvarezlqo@gmail.com.
3
Unidad de Biología Molecular, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo 11400, Uruguay. Electronic address: sandra.corre@pasteur.fr.
4
Unidad de Biología Molecular, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo 11400, Uruguay. Electronic address: pfaral@pasteur.edu.uy.
5
Unidad de Proteómica y Bioquímica Analíticas, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo 11400, Uruguay; Instituto de Investigaciones Biológicas Clemente Estable, Avenida Italia 3318, CP 11600, Montevideo, Uruguay. Electronic address: duran@pasteur.edu.uy.
6
Unidad de Proteómica y Bioquímica Analíticas, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo 11400, Uruguay; Instituto de Investigaciones Biológicas Clemente Estable, Avenida Italia 3318, CP 11600, Montevideo, Uruguay; Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. Electronic address: batthyany@pasteur.edu.uy.
7
Grupo de Química Medicinal, Laboratorio de Química Orgánica, Facultad de Ciencias-Facultad de Química, Universidad de la República, Iguá 4225, Montevideo 11400, Uruguay. Electronic address: hcerecet@fq.edu.uy.
8
Grupo de Química Medicinal, Laboratorio de Química Orgánica, Facultad de Ciencias-Facultad de Química, Universidad de la República, Iguá 4225, Montevideo 11400, Uruguay. Electronic address: megonzal@fq.edu.uy.
9
Unidad de Biología Molecular, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo 11400, Uruguay; Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. Electronic address: robello@pasteur.edu.uy.

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.

KEYWORDS:

Aldo–ketoreductases; Benznidazole; Chemical proteomics; TcAKR; Trypanosoma cruzi

PMID:
24632192
DOI:
10.1016/j.exppara.2014.03.013
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center