4E interacting protein as a potential novel drug target for nucleoside analogues in Trypanosoma brucei

Detalhes bibliográficos
Autor(a) principal: Mabille, Dorien
Data de Publicação: 2021
Outros Autores: Santos, Camila Cardoso, Hendrickx, Rik, Claes, Mathieu, Takac, Peter, Clayton, Christine, Hendrickx, Sarah, Hulpia, Fabian, Maes, Louis, Van Calenbergh, Serge, Caljon, Guy
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/50148
Resumo: University of Antwerp. Laboratory of Microbiology, Parasitology and Hygiene. Wilrijk, Belgium.
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spelling Mabille, DorienSantos, Camila CardosoHendrickx, RikClaes, MathieuTakac, PeterClayton, ChristineHendrickx, SarahHulpia, FabianMaes, LouisVan Calenbergh, SergeCaljon, Guy2021-12-03T12:11:20Z2021-12-03T12:11:20Z2021MABILLE, Dorien et al. 4E interacting protein as a potential novel drug target for nucleoside analogues in Trypanosoma brucei. Microorganisms, v. 9, n. 4, p. 1-16, 13 Apr. 2021.2076-2607https://www.arca.fiocruz.br/handle/icict/5014810.3390/microorganisms90408262076-2607engMDPIAlvo de drogasTripanossomíaseAnálogos de nucleosídeoProteína que interage com CERNAiTrypanosomiasisNucleoside analoguesRNAiDrug target4E-interacting protein4E interacting protein as a potential novel drug target for nucleoside analogues in Trypanosoma bruceiinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversity of Antwerp. Laboratory of Microbiology, Parasitology and Hygiene. Wilrijk, Belgium.University of Antwerp. Laboratory of Microbiology, Parasitology and Hygiene. Wilrijk, Belgium / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.University of Antwerp. Laboratory of Microbiology, Parasitology and Hygiene. Wilrijk, Belgium.University of Antwerp. Laboratory of Microbiology, Parasitology and Hygiene. Wilrijk, Belgium.Slovak Academy of Sciences. Institute of Zoology. Bratislava, Slovakia / Scientica, Ltd. Bratislava, Slovakia.Universität Heidelberg. Zentrum für Molekulare Biologie. DKFZ-ZMBH Alliance. Heidelberg, Germany.University of Antwerp. Laboratory of Microbiology, Parasitology and Hygiene. Wilrijk, Belgium.Ghent University. Campus Heymans. Laboratory for Medicinal Chemistry. Gent, Belgium.University of Antwerp. Laboratory of Microbiology, Parasitology and Hygiene. Wilrijk, Belgium.Ghent University. Campus Heymans. Laboratory for Medicinal Chemistry. Gent, Belgium.University of Antwerp. Laboratory of Microbiology, Parasitology and Hygiene. Wilrijk, Belgium.Human African trypanosomiasis is a neglected parasitic disease for which the current treatment options are quite limited. Trypanosomes are not able to synthesize purines de novo and thus solely depend on purine salvage from the host environment. This characteristic makes players of the purine salvage pathway putative drug targets. The activity of known nucleoside analogues such as tubercidin and cordycepin led to the development of a series of C7-substituted nucleoside analogues. Here, we use RNA interference (RNAi) libraries to gain insight into the mode-of-action of these novel nucleoside analogues. Whole-genome RNAi screening revealed the involvement of adenosine kinase and 4E interacting protein into the mode-of-action of certain antitrypanosomal nucleoside analogues. Using RNAi lines and gene-deficient parasites, 4E interacting protein was found to be essential for parasite growth and infectivity in the vertebrate host. The essential nature of this gene product and involvement in the activity of certain nucleoside analogues indicates that it represents a potential novel drug target.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/50148/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALCamilaCardoso_Santos_etal_IOC_2021.pdfCamilaCardoso_Santos_etal_IOC_2021.pdfapplication/pdf6488002https://www.arca.fiocruz.br/bitstream/icict/50148/2/CamilaCardoso_Santos_etal_IOC_2021.pdf52ac3f35ab82a0be7a30d9b6dc0aaacaMD52icict/501482022-06-24 12:19:38.048oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352022-06-24T15:19:38Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.en.fl_str_mv 4E interacting protein as a potential novel drug target for nucleoside analogues in Trypanosoma brucei
title 4E interacting protein as a potential novel drug target for nucleoside analogues in Trypanosoma brucei
spellingShingle 4E interacting protein as a potential novel drug target for nucleoside analogues in Trypanosoma brucei
Mabille, Dorien
Alvo de drogas
Tripanossomíase
Análogos de nucleosídeo
Proteína que interage com CE
RNAi
Trypanosomiasis
Nucleoside analogues
RNAi
Drug target
4E-interacting protein
title_short 4E interacting protein as a potential novel drug target for nucleoside analogues in Trypanosoma brucei
title_full 4E interacting protein as a potential novel drug target for nucleoside analogues in Trypanosoma brucei
title_fullStr 4E interacting protein as a potential novel drug target for nucleoside analogues in Trypanosoma brucei
title_full_unstemmed 4E interacting protein as a potential novel drug target for nucleoside analogues in Trypanosoma brucei
title_sort 4E interacting protein as a potential novel drug target for nucleoside analogues in Trypanosoma brucei
author Mabille, Dorien
author_facet Mabille, Dorien
Santos, Camila Cardoso
Hendrickx, Rik
Claes, Mathieu
Takac, Peter
Clayton, Christine
Hendrickx, Sarah
Hulpia, Fabian
Maes, Louis
Van Calenbergh, Serge
Caljon, Guy
author_role author
author2 Santos, Camila Cardoso
Hendrickx, Rik
Claes, Mathieu
Takac, Peter
Clayton, Christine
Hendrickx, Sarah
Hulpia, Fabian
Maes, Louis
Van Calenbergh, Serge
Caljon, Guy
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Mabille, Dorien
Santos, Camila Cardoso
Hendrickx, Rik
Claes, Mathieu
Takac, Peter
Clayton, Christine
Hendrickx, Sarah
Hulpia, Fabian
Maes, Louis
Van Calenbergh, Serge
Caljon, Guy
dc.subject.other.pt_BR.fl_str_mv Alvo de drogas
Tripanossomíase
Análogos de nucleosídeo
Proteína que interage com CE
RNAi
topic Alvo de drogas
Tripanossomíase
Análogos de nucleosídeo
Proteína que interage com CE
RNAi
Trypanosomiasis
Nucleoside analogues
RNAi
Drug target
4E-interacting protein
dc.subject.en.en.fl_str_mv Trypanosomiasis
Nucleoside analogues
RNAi
Drug target
4E-interacting protein
description University of Antwerp. Laboratory of Microbiology, Parasitology and Hygiene. Wilrijk, Belgium.
publishDate 2021
dc.date.accessioned.fl_str_mv 2021-12-03T12:11:20Z
dc.date.available.fl_str_mv 2021-12-03T12:11:20Z
dc.date.issued.fl_str_mv 2021
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv MABILLE, Dorien et al. 4E interacting protein as a potential novel drug target for nucleoside analogues in Trypanosoma brucei. Microorganisms, v. 9, n. 4, p. 1-16, 13 Apr. 2021.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/50148
dc.identifier.issn.pt_BR.fl_str_mv 2076-2607
dc.identifier.doi.pt_BR.fl_str_mv 10.3390/microorganisms9040826
dc.identifier.eissn.pt_BR.fl_str_mv 2076-2607
identifier_str_mv MABILLE, Dorien et al. 4E interacting protein as a potential novel drug target for nucleoside analogues in Trypanosoma brucei. Microorganisms, v. 9, n. 4, p. 1-16, 13 Apr. 2021.
2076-2607
10.3390/microorganisms9040826
url https://www.arca.fiocruz.br/handle/icict/50148
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/50148/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/50148/2/CamilaCardoso_Santos_etal_IOC_2021.pdf
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bitstream.checksumAlgorithm.fl_str_mv MD5
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repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv repositorio.arca@fiocruz.br
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