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)

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 > School of Infection & Immunity
• 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

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
172474		A new drug discovery pipeline for animal African trypanosomiasis	Michael Barrett	Biotechnology and Biological Sciences Research Council (BBSRC)	BB/N007999/1	III - Parasitology
170547		The Wellcome Centre for Molecular Parasitology ( Core Support )	Andrew Waters	Wellcome Trust (WELLCOTR)	104111/Z/14/ZR	III - Parasitology