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Please use this identifier to cite or link to this item: http://hdl.handle.net/10023/3043
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Title: ALDH2 mediates 5-nitrofuran activity in multiple species
Authors: Zhou, Linna
Ishizaki, Hironori
Spitzer, Michaela
Taylor, Kerrie
Temperley, Nicholas
Johnson, Stephen
Brear, Paul
Gautier, Philippe
Zeng, Zhiqiang
Mitchell, Amy
Narayan, Vikram
McNeil, Ewan
Melton, David
Smith, Terry K
Tyers, Mike
Westwood, Nicholas James
Patton, Elizabeth
Keywords: QD Chemistry
Issue Date: 27-Jul-2012
Citation: Zhou , L , Ishizaki , H , Spitzer , M , Taylor , K , Temperley , N , Johnson , S , Brear , P , Gautier , P , Zeng , Z , Mitchell , A , Narayan , V , McNeil , E , Melton , D , Smith , T K , Tyers , M , Westwood , N J & Patton , E 2012 , ' ALDH2 mediates 5-nitrofuran activity in multiple species ' Chemistry and Biology , vol 19 , no. 7 , pp. 883-892 .
Abstract: Understanding how drugs work in vivo is critical for drug design and for maximizing the potential of currently available drugs. 5-nitrofurans are a class of pro-drugs widely used to treat bacterial and trypanosome infections, but despite relative specificity 5-nitrofurans often cause serious toxic side-effects in people. Here, we use yeast, zebrafish and human in vitro systems to assess the biological activity of 5-nitrofurans, and identify a conserved interaction between aldehyde dehydrogenase (ALDH) 2 and 5-nitrofurans across these species. In addition, we show that the activity of nifurtimox, a 5-nitrofuran anti-trypanosome pro-drug, is dependent on zebrafish Aldh2 and that nifurtimox is a substrate for human ALDH2. This study reveals a conserved and biologically relevant ALDH2-5-nitrofuran interaction that may have important implications for managing the toxicity of 5nitrofuran treatment.
Version: Postprint
Status: Peer reviewed
URI: http://hdl.handle.net/10023/3043
DOI: http://dx.doi.org/10.1016/j.chembiol.2012.05.017
ISSN: 1074-5521
Type: Journal article
Rights: This is an author version of this article. The published version Copyright © 2012 Elsevier Ltd is available at www.sciencedirect.com
Appears in Collections:University of St Andrews Research
Biology Research
Chemistry Research
Biomedical Sciences Research Complex (BSRC) Research



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