Home > Research > Publications & Outputs > Fragment screening reveals salicylic hydroxamic...

Electronic data

  • Urbaniak_CRes_2014

    Rights statement: 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.

    Final published version, 1.26 MB, PDF document

    Available under license: CC BY-NC-ND

Links

Text available via DOI:

View graph of relations

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

Research output: Contribution to journalJournal articlepeer-review

Published

Standard

Fragment screening reveals salicylic hydroxamic acid as an inhibitor of Trypanosoma brucei GPI GlcNAc-PI de-N-acetylase. / Urbaniak, Michael D.; Capes, Amy S.; Crossman, Arthur; O'Neill, Sandra; Thompson, Stephen; Gilbert, Ian H.; Ferguson, Michael A. J.

In: Carbohydrate Research, Vol. 387, 31.03.2014, p. 54-58.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Urbaniak, MD, Capes, AS, Crossman, A, O'Neill, S, Thompson, S, Gilbert, IH & Ferguson, MAJ 2014, 'Fragment screening reveals salicylic hydroxamic acid as an inhibitor of Trypanosoma brucei GPI GlcNAc-PI de-N-acetylase', Carbohydrate Research, vol. 387, pp. 54-58. https://doi.org/10.1016/j.carres.2013.12.016

APA

Urbaniak, M. D., Capes, A. S., Crossman, A., O'Neill, S., Thompson, S., Gilbert, I. H., & Ferguson, M. A. J. (2014). Fragment screening reveals salicylic hydroxamic acid as an inhibitor of Trypanosoma brucei GPI GlcNAc-PI de-N-acetylase. Carbohydrate Research, 387, 54-58. https://doi.org/10.1016/j.carres.2013.12.016

Vancouver

Author

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

Bibtex

@article{82fc0daab759484b82b0e3a32fbfc2fa,
title = "Fragment screening reveals salicylic hydroxamic acid as an inhibitor of Trypanosoma brucei GPI GlcNAc-PI de-N-acetylase",
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.",
keywords = "GPI, Trypanosoma brucei , Hydroxamic acid , Inhibitor , N-Deacetylase",
author = "Urbaniak, {Michael D.} and Capes, {Amy S.} and Arthur Crossman and Sandra O'Neill and Stephen Thompson and Gilbert, {Ian H.} and Ferguson, {Michael A. J.}",
note = "Copyright {\textcopyright} 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.",
year = "2014",
month = mar,
day = "31",
doi = "10.1016/j.carres.2013.12.016",
language = "English",
volume = "387",
pages = "54--58",
journal = "Carbohydrate Research",
issn = "0008-6215",
publisher = "Elsevier BV",

}

RIS

TY - JOUR

T1 - Fragment screening reveals salicylic hydroxamic acid as an inhibitor of Trypanosoma brucei GPI GlcNAc-PI de-N-acetylase

AU - Urbaniak, Michael D.

AU - Capes, Amy S.

AU - Crossman, Arthur

AU - O'Neill, Sandra

AU - Thompson, Stephen

AU - Gilbert, Ian H.

AU - Ferguson, Michael A. J.

N1 - 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.

PY - 2014/3/31

Y1 - 2014/3/31

N2 - 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.

AB - 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.

KW - GPI

KW - Trypanosoma brucei

KW - Hydroxamic acid

KW - Inhibitor

KW - N-Deacetylase

U2 - 10.1016/j.carres.2013.12.016

DO - 10.1016/j.carres.2013.12.016

M3 - Journal article

C2 - 24589444

VL - 387

SP - 54

EP - 58

JO - Carbohydrate Research

JF - Carbohydrate Research

SN - 0008-6215

ER -