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

Peter E. Cockram; Emily A. Dickie; Michael P. Barrett; Terry K. Smith

doi:10.1371/journal.pntd.0008928

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

Peter E. Cockram, Emily A. Dickie, Michael P. Barrett, Terry K. Smith^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	e0008928
Number of pages	19
Journal	PLoS Neglected Tropical Diseases
Volume	14
Issue number	12
DOIs	https://doi.org/10.1371/journal.pntd.0008928
Publication status	Published - 4 Dec 2020

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10.1371/journal.pntd.0008928Licence: CC BY

Cockram_2020_PloS_halogenated_CC
Copyright: © 2020 Cockram et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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title = "Halogenated tryptophan derivatives disrupt essential transamination mechanisms in bloodstream form Trypanosoma brucei",

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.",

author = "Cockram, {Peter E.} and Dickie, {Emily A.} and Barrett, {Michael P.} and Smith, {Terry K.}",

note = "Funding for this work was provided by the University of St Andrews; EPSRC: EP/J500549/1 (TKS); University of Glasgow (MPB); BBSRC: BB/N007999/1 (MPB); Wellcome: 104111/Z/14/Z. ",

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AU - Barrett, Michael P.

AU - Smith, Terry K.

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N2 - 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.

AB - 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.

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DO - 10.1371/journal.pntd.0008928

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ER -

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

Abstract

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