Evidence map›Paper›PMID 24989497›Full record

ArticleAngewandte Chemie (International ed. in English)2014

A protein-based pentavalent inhibitor of the cholera toxin B-subunit.

Thomas R Branson, Tom E McAllister, Jaime Garcia-Hartjes, Martin A Fascione, James F Ross, Stuart L Warriner, Tom Wennekes, Han Zuilhof, W Bruce Turnbull

Open access · bronzeAbstract read
In one paragraph

Article in Angewandte Chemie (International ed. in English), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
6.5field-weighted citation impact, top 2% 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

31 citing papers in PubMed, 66 citations in OpenAlex.

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  19. Synthesis of GbAngewandte Chemie (International ed. in English) · 2019
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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

9 authors at 3 institutions in 3 countries.

Thomas R BransonSchool of Chemistry and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT (UK).
Tom E McAllister
Jaime Garcia-Hartjes
Martin A Fascione
James F Ross
Stuart L Warriner
Tom Wennekes
Han Zuilhof
W Bruce Turnbull
University of Leeds · GBWageningen University & Research · NLKing Abdulaziz University · SA

Funding

Wellcome Trust 089308/Z/09/ZWellcome Trust 094232/Z/10/Z
6 · The paper itself

Abstract

Protein toxins produced by bacteria are the cause of many life-threatening diarrheal diseases. Many of these toxins, including cholera toxin (CT), enter the cell by first binding to glycolipids in the cell membrane. Inhibiting these multivalent protein/carbohydrate interactions would prevent the toxin from entering cells and causing diarrhea. Here we demonstrate that the site-specific modification of a protein scaffold, which is perfectly matched in both size and valency to the target toxin, provides a convenient route to an effective multivalent inhibitor. The resulting pentavalent neoglycoprotein displays an inhibition potency (IC50) of 104 pM for the CT B-subunit (CTB), which is the most potent pentavalent inhibitor for this target reported thus far. Complexation of the inhibitor and CTB resulted in a protein heterodimer. This inhibition strategy can potentially be applied to many multivalent receptors and also opens up new possibilities for protein assembly strategies.

Indexed as

BacteriaBinding SitesCarbohydratesCholera ToxinGlycoproteinsModels, MolecularProteinsCarbohydratesCholera ToxinGlycoproteinsProteinscarbohydratesglycoproteinsmultivalencyprotein modificationsprotein structures

Identifiers

PMID24989497
PMCPMC4499251
OpenAlexW2166133779

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.