Publication
Title
4E interacting protein as a potential novel drug target for nucleoside analogues in Trypanosoma brucei
Author
Abstract
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.
Language
English
Source (journal)
Microorganisms
Publication
2021
ISSN
2076-2607
DOI
10.3390/MICROORGANISMS9040826
Volume/pages
9 :4 (2021) , 18 p.
Article Reference
826
ISI
000643295800001
Pubmed ID
33924674
Medium
E-only publicatie
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Project info
Exploring and targeting the kinome of immune cells exposed to African trypanosomes.
Modified 7-deazapurine nucleoside analogues for the treatment of human African trypanosomiasis: towards a strong proof-of-concept.
Veterinary and human parasitology.
Infla-Med: Fundamental and translational research into targets for the treatment of inflammatory diseases.
Exploring and targeting the kinome of immune cells exposed to protozoan parasites.
Control of sleeping sickness and leishmaniasis: from an insect bite to effective treatment.
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identifier
Creation 14.04.2021
Last edited 02.10.2024
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