title: 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.affiliation: Unidad de Biología Molecular, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo 11400, Uruguay. Electronic address: atrochine@gmail.com.
authors.forename: Andrea
authors.initials: A
authors.lastname: Trochine
authors.affiliation: 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.
authors.forename: Guzmán
authors.initials: G
authors.lastname: Alvarez
authors.affiliation: Unidad de Biología Molecular, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo 11400, Uruguay. Electronic address: sandra.corre@pasteur.fr.
authors.forename: Sandra
authors.initials: S
authors.lastname: Corre
authors.affiliation: Unidad de Biología Molecular, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo 11400, Uruguay. Electronic address: pfaral@pasteur.edu.uy.
authors.forename: Paula
authors.initials: P
authors.lastname: Faral-Tello
authors.affiliation: 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.
authors.forename: Rosario
authors.initials: R
authors.lastname: Durán
authors.affiliation: 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.
authors.forename: Carlos I
authors.initials: CI
authors.lastname: Batthyany
authors.affiliation: 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.
authors.forename: Hugo
authors.initials: H
authors.lastname: Cerecetto
authors.affiliation: 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.
authors.forename: Mercedes
authors.initials: M
authors.lastname: González
authors.affiliation: 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.
authors.forename: Carlos
authors.initials: C
authors.lastname: Robello
mesh_terms: D000449:Aldehyde Reductase / Q000378:metabolism; D000074408:Aldo-Keto Reductases; D002846:Chromatography, Affinity; D004591:Electrophoresis, Polyacrylamide Gel; D008863:Microspheres; D009593:Nitroimidazoles / Q000138:chemical synthesis / Q000378:metabolism*; D040901:Proteomics; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism*; D012685:Sepharose / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014344:Trypanocidal Agents / Q000378:metabolism*; D014349:Trypanosoma cruzi / Q000201:enzymology / Q000378:metabolism*; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism
chemical_list: D009593:Nitroimidazoles; D015800:Protozoan Proteins; D014344:Trypanocidal Agents; D014404:Tubulin; D012685:Sepharose; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase; C009999:benzonidazole
keywords: Aldo–ketoreductases; Benznidazole; Chemical proteomics; TcAKR; Trypanosoma cruzi