Metacaspases, Autophagins and Metallocarboxypeptidases: Potential New Targets for Chemotherapy of the Trypanosomiases
- Autores
- Alvarez, Vanina Eder; Niemirowicz, Gabriela Teresa; Cazzulo, Juan Jose
- Año de publicación
- 2013
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- During the last decade, de novo drug discovery approaches have come into focus due to the increased number of parasite pathogen genomes sequenced and the subsequent availability of genome-scale functional datasets. In order to prioritize target proteins, these approaches consider traits commonly thought to be desirable in a drug target, including essentiality, druggability (whether drug-like molecules are likely to interact with the target), assayability, importance in lifecycle stages of the pathogen relevant to human health, and specificity (i.e. the target is absent from, or substantially different in, the host). Proteases from protozoan parasites have become popular drug targets since these enzymes accomplish both housekeeping tasks common to many eukaryotes as well as functions highly specific to the parasite life style. Trypanosoma cruzi, the parasitic flagellate, agent of Chagas Disease, contains several cysteine, serine, threonine and metallo proteinases. This review will deal with peculiar families described in this parasite. Among them, two eukaryote homologues of the carboxypeptidases Taq are promising targets due to their particular phylogenetic distribution. Also absent in metazoans, metacaspases are essential peptidases playing important roles in cell growth, death and differentiation of trypanosomatids. Finally, autophagins are involved in the regulation of a conserved degradative pathway, the autophagy pathway, and result important for parasite survival under nutritional stress conditions and differentiation. Although so far there are no specific inhibitors for these families, the increasing knowledge of their biochemical properties, including substrate specificity, crystal structure, and biological functions, is an essential step towards the development of inhibitors.
Fil: Alvarez, Vanina Eder. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Niemirowicz, Gabriela Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Cazzulo, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina - Materia
-
Autophagin
Carboxypeptidase
Chagas Disease
Inhibitor
Metacaspase
Metallopeptidase
Cysteine Proteinase
Peptidase
Trypanosoma Brucei
Trypanosoma Cruzi - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/24384
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Metacaspases, Autophagins and Metallocarboxypeptidases: Potential New Targets for Chemotherapy of the TrypanosomiasesAlvarez, Vanina EderNiemirowicz, Gabriela TeresaCazzulo, Juan JoseAutophaginCarboxypeptidaseChagas DiseaseInhibitorMetacaspaseMetallopeptidaseCysteine ProteinasePeptidaseTrypanosoma BruceiTrypanosoma Cruzihttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3During the last decade, de novo drug discovery approaches have come into focus due to the increased number of parasite pathogen genomes sequenced and the subsequent availability of genome-scale functional datasets. In order to prioritize target proteins, these approaches consider traits commonly thought to be desirable in a drug target, including essentiality, druggability (whether drug-like molecules are likely to interact with the target), assayability, importance in lifecycle stages of the pathogen relevant to human health, and specificity (i.e. the target is absent from, or substantially different in, the host). Proteases from protozoan parasites have become popular drug targets since these enzymes accomplish both housekeeping tasks common to many eukaryotes as well as functions highly specific to the parasite life style. Trypanosoma cruzi, the parasitic flagellate, agent of Chagas Disease, contains several cysteine, serine, threonine and metallo proteinases. This review will deal with peculiar families described in this parasite. Among them, two eukaryote homologues of the carboxypeptidases Taq are promising targets due to their particular phylogenetic distribution. Also absent in metazoans, metacaspases are essential peptidases playing important roles in cell growth, death and differentiation of trypanosomatids. Finally, autophagins are involved in the regulation of a conserved degradative pathway, the autophagy pathway, and result important for parasite survival under nutritional stress conditions and differentiation. Although so far there are no specific inhibitors for these families, the increasing knowledge of their biochemical properties, including substrate specificity, crystal structure, and biological functions, is an essential step towards the development of inhibitors.Fil: Alvarez, Vanina Eder. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Niemirowicz, Gabriela Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Cazzulo, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaBentham Science Publishers2013-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/24384Alvarez, Vanina Eder; Niemirowicz, Gabriela Teresa; Cazzulo, Juan Jose; Metacaspases, Autophagins and Metallocarboxypeptidases: Potential New Targets for Chemotherapy of the Trypanosomiases; Bentham Science Publishers; Current Medicinal Chemistry; 20; 25; 4-2013; 3069-30770929-8673CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.2174/0929867311320250004info:eu-repo/semantics/altIdentifier/url/http://www.eurekaselect.com/112888/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:46:11Zoai:ri.conicet.gov.ar:11336/24384instacron: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:34982025-09-29 09:46:11.931CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Metacaspases, Autophagins and Metallocarboxypeptidases: Potential New Targets for Chemotherapy of the Trypanosomiases |
title |
Metacaspases, Autophagins and Metallocarboxypeptidases: Potential New Targets for Chemotherapy of the Trypanosomiases |
spellingShingle |
Metacaspases, Autophagins and Metallocarboxypeptidases: Potential New Targets for Chemotherapy of the Trypanosomiases Alvarez, Vanina Eder Autophagin Carboxypeptidase Chagas Disease Inhibitor Metacaspase Metallopeptidase Cysteine Proteinase Peptidase Trypanosoma Brucei Trypanosoma Cruzi |
title_short |
Metacaspases, Autophagins and Metallocarboxypeptidases: Potential New Targets for Chemotherapy of the Trypanosomiases |
title_full |
Metacaspases, Autophagins and Metallocarboxypeptidases: Potential New Targets for Chemotherapy of the Trypanosomiases |
title_fullStr |
Metacaspases, Autophagins and Metallocarboxypeptidases: Potential New Targets for Chemotherapy of the Trypanosomiases |
title_full_unstemmed |
Metacaspases, Autophagins and Metallocarboxypeptidases: Potential New Targets for Chemotherapy of the Trypanosomiases |
title_sort |
Metacaspases, Autophagins and Metallocarboxypeptidases: Potential New Targets for Chemotherapy of the Trypanosomiases |
dc.creator.none.fl_str_mv |
Alvarez, Vanina Eder Niemirowicz, Gabriela Teresa Cazzulo, Juan Jose |
author |
Alvarez, Vanina Eder |
author_facet |
Alvarez, Vanina Eder Niemirowicz, Gabriela Teresa Cazzulo, Juan Jose |
author_role |
author |
author2 |
Niemirowicz, Gabriela Teresa Cazzulo, Juan Jose |
author2_role |
author author |
dc.subject.none.fl_str_mv |
Autophagin Carboxypeptidase Chagas Disease Inhibitor Metacaspase Metallopeptidase Cysteine Proteinase Peptidase Trypanosoma Brucei Trypanosoma Cruzi |
topic |
Autophagin Carboxypeptidase Chagas Disease Inhibitor Metacaspase Metallopeptidase Cysteine Proteinase Peptidase Trypanosoma Brucei Trypanosoma Cruzi |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.3 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
During the last decade, de novo drug discovery approaches have come into focus due to the increased number of parasite pathogen genomes sequenced and the subsequent availability of genome-scale functional datasets. In order to prioritize target proteins, these approaches consider traits commonly thought to be desirable in a drug target, including essentiality, druggability (whether drug-like molecules are likely to interact with the target), assayability, importance in lifecycle stages of the pathogen relevant to human health, and specificity (i.e. the target is absent from, or substantially different in, the host). Proteases from protozoan parasites have become popular drug targets since these enzymes accomplish both housekeeping tasks common to many eukaryotes as well as functions highly specific to the parasite life style. Trypanosoma cruzi, the parasitic flagellate, agent of Chagas Disease, contains several cysteine, serine, threonine and metallo proteinases. This review will deal with peculiar families described in this parasite. Among them, two eukaryote homologues of the carboxypeptidases Taq are promising targets due to their particular phylogenetic distribution. Also absent in metazoans, metacaspases are essential peptidases playing important roles in cell growth, death and differentiation of trypanosomatids. Finally, autophagins are involved in the regulation of a conserved degradative pathway, the autophagy pathway, and result important for parasite survival under nutritional stress conditions and differentiation. Although so far there are no specific inhibitors for these families, the increasing knowledge of their biochemical properties, including substrate specificity, crystal structure, and biological functions, is an essential step towards the development of inhibitors. Fil: Alvarez, Vanina Eder. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina Fil: Niemirowicz, Gabriela Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina Fil: Cazzulo, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina |
description |
During the last decade, de novo drug discovery approaches have come into focus due to the increased number of parasite pathogen genomes sequenced and the subsequent availability of genome-scale functional datasets. In order to prioritize target proteins, these approaches consider traits commonly thought to be desirable in a drug target, including essentiality, druggability (whether drug-like molecules are likely to interact with the target), assayability, importance in lifecycle stages of the pathogen relevant to human health, and specificity (i.e. the target is absent from, or substantially different in, the host). Proteases from protozoan parasites have become popular drug targets since these enzymes accomplish both housekeeping tasks common to many eukaryotes as well as functions highly specific to the parasite life style. Trypanosoma cruzi, the parasitic flagellate, agent of Chagas Disease, contains several cysteine, serine, threonine and metallo proteinases. This review will deal with peculiar families described in this parasite. Among them, two eukaryote homologues of the carboxypeptidases Taq are promising targets due to their particular phylogenetic distribution. Also absent in metazoans, metacaspases are essential peptidases playing important roles in cell growth, death and differentiation of trypanosomatids. Finally, autophagins are involved in the regulation of a conserved degradative pathway, the autophagy pathway, and result important for parasite survival under nutritional stress conditions and differentiation. Although so far there are no specific inhibitors for these families, the increasing knowledge of their biochemical properties, including substrate specificity, crystal structure, and biological functions, is an essential step towards the development of inhibitors. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-04 |
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/11336/24384 Alvarez, Vanina Eder; Niemirowicz, Gabriela Teresa; Cazzulo, Juan Jose; Metacaspases, Autophagins and Metallocarboxypeptidases: Potential New Targets for Chemotherapy of the Trypanosomiases; Bentham Science Publishers; Current Medicinal Chemistry; 20; 25; 4-2013; 3069-3077 0929-8673 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/24384 |
identifier_str_mv |
Alvarez, Vanina Eder; Niemirowicz, Gabriela Teresa; Cazzulo, Juan Jose; Metacaspases, Autophagins and Metallocarboxypeptidases: Potential New Targets for Chemotherapy of the Trypanosomiases; Bentham Science Publishers; Current Medicinal Chemistry; 20; 25; 4-2013; 3069-3077 0929-8673 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.2174/0929867311320250004 info:eu-repo/semantics/altIdentifier/url/http://www.eurekaselect.com/112888/ |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Bentham Science Publishers |
publisher.none.fl_str_mv |
Bentham Science Publishers |
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reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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13.070432 |