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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/24384

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oai_identifier_str oai:ri.conicet.gov.ar:11336/24384
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 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
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
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