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The trypanosome alternative oxidase: a potential drug target?

Published online by Cambridge University Press:  29 November 2016

STEFANIE K. MENZIES Open the ORCID record for STEFANIE K. MENZIES [Opens in a new window] ,
LINDSAY B. TULLOCH ,
GORDON J. FLORENCE  and
TERRY K. SMITH
STEFANIE K. MENZIES
Affiliation:
Biomedical Sciences Research Complex, University of St Andrews, St Andrews, Fife, Scotland KY16 9ST, UK
LINDSAY B. TULLOCH
Affiliation:
Biomedical Sciences Research Complex, University of St Andrews, St Andrews, Fife, Scotland KY16 9ST, UK
GORDON J. FLORENCE
Affiliation:
Biomedical Sciences Research Complex, University of St Andrews, St Andrews, Fife, Scotland KY16 9ST, UK
TERRY K. SMITH*
Affiliation:
Biomedical Sciences Research Complex, University of St Andrews, St Andrews, Fife, Scotland KY16 9ST, UK
*
*Corresponding author. Biomedical Sciences Research Complex, University of St Andrews, St Andrews, Fife, Scotland KY16 9ST, UK. E-mail: tks1@st-andrews.ac.uk
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Summary

New drugs against Trypanosoma brucei, the causative agent of Human African Trypanosomiasis, are urgently needed to replace the highly toxic and largely ineffective therapies currently used. The trypanosome alternative oxidase (TAO) is an essential and unique mitochondrial protein in these parasites and is absent from mammalian mitochondria, making it an attractive drug target. The structure and function of the protein are now well characterized, with several inhibitors reported in the literature, which show potential as clinical drug candidates. In this review, we provide an update on the functional activity and structural aspects of TAO. We then discuss TAO inhibitors reported to date, problems encountered with in vivo testing of these compounds, and discuss the future of TAO as a therapeutic target.

Keywords

Trypanosome alternative oxidasedrug discoverychemotherapyhuman African trypanosomiasissleeping sicknessTrypanosoma brucei
Type
Special Issue Review
Information
Parasitology , Volume 145 , Special Issue 2: Microbial protein targets: towards understanding and intervention , February 2018 , pp. 175 - 183
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Copyright
Copyright © Cambridge University Press 2016 

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References

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