Halogenated tryptophan derivatives disrupt essential transamination mechanisms in bloodstream form Trypanosoma brucei

Cockram, P. E., Dickie, E. A., Barrett, M. P. and Smith, T. K. (2020) Halogenated tryptophan derivatives disrupt essential transamination mechanisms in bloodstream form Trypanosoma brucei. PLoS Neglected Tropical Diseases, 14(12), e0008928. (doi: 10.1371/journal.pntd.0008928) (PMID:33275612) (PMCID:PMC7744056)

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Abstract

Amino acid metabolism within Trypanosoma brucei, the causative agent of human African trypanosomiasis, is critical for parasite survival and virulence. Of these metabolic processes, the transamination of aromatic amino acids is one of the most important. In this study, a series of halogenated tryptophan analogues were investigated for their anti-parasitic potency. Several of these analogues showed significant trypanocidal activity. Metabolomics analysis of compound-treated parasites revealed key differences occurring within aromatic amino acid metabolism, particularly within the widely reported and essential transamination processes of this parasite.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Dickie, Dr Emily and Barrett, Professor Michael
Creator Roles:
Dickie, E. A.Investigation, Methodology, Writing – original draft
Barrett, M. P.Funding acquisition, Supervision, Writing – review and editing
Authors: Cockram, P. E., Dickie, E. A., Barrett, M. P., and Smith, T. K.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:PLoS Neglected Tropical Diseases
Publisher:Public Library of Science
ISSN:1935-2727
ISSN (Online):1935-2735
Published Online:04 December 2020
Copyright Holders:Copyright © 2020 Cockram et al.
First Published:First published in PLoS Neglected Tropical Diseases 14(12): e0008928
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172474A new drug discovery pipeline for animal African trypanosomiasisMichael BarrettBiotechnology and Biological Sciences Research Council (BBSRC)BB/N007999/1III - Parasitology
170547The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOTR)104111/Z/14/ZRIII - Parasitology