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

dc.creatorMabille, Dorien
dc.creatorSantos, Camila Cardoso
dc.creatorHendrickx, Rik
dc.creatorClaes, Mathieu
dc.creatorTakac, Peter
dc.creatorClayton, Christine
dc.creatorHendrickx, Sarah
dc.creatorHulpia, Fabian
dc.creatorMaes, Louis
dc.creatorVan Calenbergh, Serge
dc.creatorCaljon, Guy
dc.date2021-12-03T12:11:20Z
dc.date2021-12-03T12:11:20Z
dc.date2021
dc.date.accessioned2023-09-26T20:13:44Z
dc.date.available2023-09-26T20:13:44Z
dc.identifierMABILLE, 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.identifier2076-2607
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/50148
dc.identifier10.3390/microorganisms9040826
dc.identifier2076-2607
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8851920
dc.descriptionHuman 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherMDPI
dc.rightsopen access
dc.subjectAlvo de drogas
dc.subjectTripanossomíase
dc.subjectAnálogos de nucleosídeo
dc.subjectProteína que interage com CE
dc.subjectRNAi
dc.subjectTrypanosomiasis
dc.subjectNucleoside analogues
dc.subjectRNAi
dc.subjectDrug target
dc.subject4E-interacting protein
dc.title4E interacting protein as a potential novel drug target for nucleoside analogues in Trypanosoma brucei
dc.typeArticle


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