Fragment screening reveals salicylic hydroxamic acid as an inhibitor of Trypanosoma brucei GPI GlcNAc-PI de-N-acetylase

Urbaniak, Michael D. and Capes, Amy S. and Crossman, Arthur and O'Neill, Sandra and Thompson, Stephen and Gilbert, Ian H. and Ferguson, Michael A. J. (2014) Fragment screening reveals salicylic hydroxamic acid as an inhibitor of Trypanosoma brucei GPI GlcNAc-PI de-N-acetylase. Carbohydrate Research, 387. pp. 54-58. ISSN 0008-6215

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Abstract

The zinc-metalloenzyme GlcNAc-PI de-N-acetylase is essential for the biosynthesis of mature GPI anchors and has been genetically validated in the bloodstream form of Trypanosoma brucei, which causes African sleeping sickness. We screened a focused library of zinc-binding fragments and identified salicylic hydroxamic acid as a GlcNAc-PI de-N-acetylase inhibitor with high ligand efficiency. This is the first small molecule inhibitor reported for the trypanosome GPI pathway. Investigating the structure activity relationship revealed that hydroxamic acid and 2-OH are essential for potency, and that substitution is tolerated at the 4- and 5-positions.

Item Type:
Journal Article
Journal or Publication Title:
Carbohydrate Research
Additional Information:
Copyright © 2013 Elsevier Ltd. All rights reserved. This article is distributed under the terms of the Creative Commons Attribution-Noncommercial-No Derivative Works License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/1600/1602
Subjects:
ID Code:
69492
Deposited By:
Deposited On:
27 May 2014 08:43
Refereed?:
Yes
Published?:
Published
Last Modified:
12 Jul 2020 04:42