Evidence map›Paper›PMID 24589444›Full record

ArticleCarbohydrate research2014

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

Michael D Urbaniak, Amy S Capes, Arthur Crossman, Sandra O'Neill, Stephen Thompson, Ian H Gilbert, Michael A J Ferguson

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Carbohydrate research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact, top 85% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
  2. Compounds targeting GPI biosynthesis orComputational and structural biotechnology journal · 2022
    Article
  3. Article
  4. Article
  5. Targeting the GPI biosynthetic pathway.Pathogens and global health · 2018
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Michael D UrbaniakDivision of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
Amy S CapesDivision of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
Arthur CrossmanDivision of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
Sandra O'NeillDivision of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
Stephen ThompsonDivision of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
Ian H GilbertDivision of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK. Electronic address: i.h.gilbert@dundee.ac.uk.
Michael A J FergusonDivision of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK. Electronic address: m.a.j.ferguson@dundee.ac.uk.
University of Dundee · GB

Funding

Medical Research CouncilWellcome Trust 077705Wellcome Trust 085622
6 · The paper itself

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.

Indexed as

AmidohydrolasesHumansHydroxamic AcidsProtein BindingSalicylatesSmall Molecule LibrariesStructure-Activity RelationshipSubstrate SpecificityTrypanosoma brucei bruceiTrypanosomiasis, AfricanZincAmidohydrolasesHydroxamic AcidsN-acetylglucosaminyl-phosphatidylinositol de-N-acetylaseSalicylatesSmall Molecule LibrariesZincGPIHydroxamic acidInhibitorN-DeacetylaseTrypanosoma brucei

Identifiers

PMID24589444
PMCPMC3991331
OpenAlexW2131595357

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.