Trypanosoma cruzi chemical proteomics using immobilized benznidazole

Autores
Trochine, Andrea; Alvarez, Guzmán; Corre, Sandra; Faral Tello, Paula; Durán, Rosario; Batthyany, Carlos I.; Cerecetto, Hugo; Gonzalez, Mercedes; Robello, Carlos
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Trochine, Andrea. Instituto Pasteur de Montevideo. Unidad de Biologia Molecular; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Patagonia Norte. Instituto de Investigación en Biodiversidad y Medioambiente; Argentina
Fil: Alvarez, Guzmán. Universidad de la República. Facultad de Ciencias; Uruguay
Fil: Corre, Sandra. Instituto Pasteur de Montevideo. Unidad de Biologia Molecular; Uruguay
Fil: Faral Tello, Paula. Instituto Pasteur de Montevideo. Unidad de Biologia Molecular; Uruguay
Fil: Durán, Rosario. Instituto Pasteur de Montevideo; Uruguay
Fil: Batthyany, Carlos I.. Instituto Pasteur de Montevideo; Uruguay. Instituto de Investigaciones Biologicas "Clemente Estable"; Uruguay
Fil: Cerecetto, Hugo. Universidad de la República. Facultad de Ciencias; Uruguay. Instituto de Investigaciones Biologicas "Clemente Estable"; Uruguay
Fil: Gonzalez, Mercedes. Universidad de la República. Facultad de Ciencias; Uruguay
Fil: Robello, Carlos. Instituto Pasteur de Montevideo. Unidad de Biologia Molecular; Uruguay. Universidad de la Republica; Uruguay
Materia
Benznidazole
Trypanosoma Cruzi
Chemical Proteomics
Aldo-Ketoreductases
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/11966
Acceder
id CONICETDig_bed8cf1da3732dc7e8a3d0754062954d
oai_identifier_str oai:ri.conicet.gov.ar:11336/11966
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Trypanosoma cruzi chemical proteomics using immobilized benznidazoleTrochine, AndreaAlvarez, GuzmánCorre, SandraFaral Tello, PaulaDurán, RosarioBatthyany, Carlos I.Cerecetto, HugoGonzalez, MercedesRobello, CarlosBenznidazoleTrypanosoma CruziChemical ProteomicsAldo-Ketoreductaseshttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Benznidazole (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.Fil: Trochine, Andrea. Instituto Pasteur de Montevideo. Unidad de Biologia Molecular; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Patagonia Norte. Instituto de Investigación en Biodiversidad y Medioambiente; ArgentinaFil: Alvarez, Guzmán. Universidad de la República. Facultad de Ciencias; UruguayFil: Corre, Sandra. Instituto Pasteur de Montevideo. Unidad de Biologia Molecular; UruguayFil: Faral Tello, Paula. Instituto Pasteur de Montevideo. Unidad de Biologia Molecular; UruguayFil: Durán, Rosario. Instituto Pasteur de Montevideo; UruguayFil: Batthyany, Carlos I.. Instituto Pasteur de Montevideo; Uruguay. Instituto de Investigaciones Biologicas "Clemente Estable"; UruguayFil: Cerecetto, Hugo. Universidad de la República. Facultad de Ciencias; Uruguay. Instituto de Investigaciones Biologicas "Clemente Estable"; UruguayFil: Gonzalez, Mercedes. Universidad de la República. Facultad de Ciencias; UruguayFil: Robello, Carlos. Instituto Pasteur de Montevideo. Unidad de Biologia Molecular; Uruguay. Universidad de la Republica; UruguayElsevier2014-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/11966Trochine, Andrea; Alvarez, Guzmán; Corre, Sandra; Faral Tello, Paula; Durán, Rosario; et al.; Trypanosoma cruzi chemical proteomics using immobilized benznidazole; Elsevier; Experimental Parasitology; 140; 3-2014; 33-380014-4894enginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.exppara.2014.03.013info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0014489414000472info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:01:19Zoai:ri.conicet.gov.ar:11336/11966instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:01:19.598CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Trypanosoma cruzi chemical proteomics using immobilized benznidazole
title Trypanosoma cruzi chemical proteomics using immobilized benznidazole
spellingShingle Trypanosoma cruzi chemical proteomics using immobilized benznidazole
Trochine, Andrea
Benznidazole
Trypanosoma Cruzi
Chemical Proteomics
Aldo-Ketoreductases
title_short Trypanosoma cruzi chemical proteomics using immobilized benznidazole
title_full Trypanosoma cruzi chemical proteomics using immobilized benznidazole
title_fullStr Trypanosoma cruzi chemical proteomics using immobilized benznidazole
title_full_unstemmed Trypanosoma cruzi chemical proteomics using immobilized benznidazole
title_sort Trypanosoma cruzi chemical proteomics using immobilized benznidazole
dc.creator.none.fl_str_mv Trochine, Andrea
Alvarez, Guzmán
Corre, Sandra
Faral Tello, Paula
Durán, Rosario
Batthyany, Carlos I.
Cerecetto, Hugo
Gonzalez, Mercedes
Robello, Carlos
author Trochine, Andrea
author_facet Trochine, Andrea
Alvarez, Guzmán
Corre, Sandra
Faral Tello, Paula
Durán, Rosario
Batthyany, Carlos I.
Cerecetto, Hugo
Gonzalez, Mercedes
Robello, Carlos
author_role author
author2 Alvarez, Guzmán
Corre, Sandra
Faral Tello, Paula
Durán, Rosario
Batthyany, Carlos I.
Cerecetto, Hugo
Gonzalez, Mercedes
Robello, Carlos
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Benznidazole
Trypanosoma Cruzi
Chemical Proteomics
Aldo-Ketoreductases
topic Benznidazole
Trypanosoma Cruzi
Chemical Proteomics
Aldo-Ketoreductases
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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.
Fil: Trochine, Andrea. Instituto Pasteur de Montevideo. Unidad de Biologia Molecular; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Patagonia Norte. Instituto de Investigación en Biodiversidad y Medioambiente; Argentina
Fil: Alvarez, Guzmán. Universidad de la República. Facultad de Ciencias; Uruguay
Fil: Corre, Sandra. Instituto Pasteur de Montevideo. Unidad de Biologia Molecular; Uruguay
Fil: Faral Tello, Paula. Instituto Pasteur de Montevideo. Unidad de Biologia Molecular; Uruguay
Fil: Durán, Rosario. Instituto Pasteur de Montevideo; Uruguay
Fil: Batthyany, Carlos I.. Instituto Pasteur de Montevideo; Uruguay. Instituto de Investigaciones Biologicas "Clemente Estable"; Uruguay
Fil: Cerecetto, Hugo. Universidad de la República. Facultad de Ciencias; Uruguay. Instituto de Investigaciones Biologicas "Clemente Estable"; Uruguay
Fil: Gonzalez, Mercedes. Universidad de la República. Facultad de Ciencias; Uruguay
Fil: Robello, Carlos. Instituto Pasteur de Montevideo. Unidad de Biologia Molecular; Uruguay. Universidad de la Republica; Uruguay
description 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.
publishDate 2014
dc.date.none.fl_str_mv 2014-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/11966
Trochine, Andrea; Alvarez, Guzmán; Corre, Sandra; Faral Tello, Paula; Durán, Rosario; et al.; Trypanosoma cruzi chemical proteomics using immobilized benznidazole; Elsevier; Experimental Parasitology; 140; 3-2014; 33-38
0014-4894
url http://hdl.handle.net/11336/11966
identifier_str_mv Trochine, Andrea; Alvarez, Guzmán; Corre, Sandra; Faral Tello, Paula; Durán, Rosario; et al.; Trypanosoma cruzi chemical proteomics using immobilized benznidazole; Elsevier; Experimental Parasitology; 140; 3-2014; 33-38
0014-4894
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.exppara.2014.03.013
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0014489414000472
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842269690245677056
score 13.13397

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