Evidence map›Paper›PMID 24060167›Full record

ArticleAnalytical chemistry2013

Development of a capillary electrophoresis platform for identifying inhibitors of protein-protein interactions.

Jennifer N Rauch, Jing Nie, Tonia J Buchholz, Jason E Gestwicki, Robert T Kennedy

Open access · greenAbstract read
In one paragraph

Article in Analytical chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

13 citing papers in PubMed, 31 citations in OpenAlex.

  1. Review
  2. Article
  3. Label-free methods for opticalPhysical chemistry chemical physics : PCCP · 2021
    Review
  4. Review
  5. Article
  6. Article
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  8. Article
  9. Review
  10. Article
  11. Article
  12. Microfluidics: reframing biological enquiry.Nature reviews. Molecular cell biology · 2015
    Review
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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

5 authors at 1 institution in 1 country.

Jennifer N RauchDepartment of Biological Chemistry, ‡Department of Chemistry, and the§ Life Sciences Institute, University of Michigan , Ann Arbor, Michigan 48109, United States.
Jing Nie
Tonia J Buchholz
Jason E Gestwicki
Robert T Kennedy
University of Michigan–Ann Arbor · US

Funding

Molecular Chaperones and Small MoleculesR01NS059690 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jason E Gestwicki · 2008 to 2026
$7.9M
High throughput mass spectrometry and electrophoresis assay systemsR01GM102236 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KENNEDY, ROBERT T · 2012 to 2015
$1.1M
Holographic control of neural ensembles during sensationF32NS095690 · NINDS · UNIVERSITY OF CALIFORNIA BERKELEY · PI MARDINLY, ALAN ROBERT · 2015 to 2017
$168k
NIGMS NIH HHS GM102236NIGMS NIH HHS R01 GM102236NINDS NIH HHS F32 NS095690NINDS NIH HHS NS095690NINDS NIH HHS R01 NS059690
6 · The paper itself

Abstract

Methods for identifying chemical inhibitors of protein-protein interactions (PPIs) are often prone to discovery of false positives, particularly those caused by molecules that induce protein aggregation. Thus, there is interest in developing new platforms that might allow earlier identification of these problematic compounds. Capillary electrophoresis (CE) has been evaluated as a method to screen for PPI inhibitors using the challenging system of Hsp70 interacting with its co-chaperone Bag3. In the method, Hsp70 is labeled with a fluorophore, mixed with Bag3, and the resulting bound and free Hsp70 are separated and detected by CE with laser-induced fluorescence detection. The method used a chemically modified CE capillary to prevent protein adsorption. Inhibitors of the Hsp70-Bag3 interaction were detected by observing a reduction in the bound-to-free ratio. The method was used to screen a library of 3443 compounds, and the results were compared to those from a flow cytometry protein interaction assay. CE was found to produce a lower hit rate with more compounds that were reconfirmed in subsequent testing, suggesting greater specificity. This finding was attributed to the use of electropherograms to detect artifacts such as aggregators and to differences in protein modifications required to perform the different assays. Increases in throughput are required to make the CE method suitable for primary screens, but at the current stage of development it is attractive as a secondary screen to test hits found by higher-throughput methods.

Indexed as

Adaptor Proteins, Signal TransducingApoptosis Regulatory ProteinsArtifactsDrug Evaluation, PreclinicalElectrophoresis, CapillaryFluorescent DyesHSP70 Heat-Shock ProteinsHumansProtein BindingSmall Molecule LibrariesAdaptor Proteins, Signal TransducingApoptosis Regulatory ProteinsBAG3 protein, humanFluorescent DyesHSP70 Heat-Shock ProteinsSmall Molecule Libraries

Identifiers

PMID24060167
PMCPMC3845662
OpenAlexW2078267500

What OpenQuestion holds

Textmetadata
LicenceTDM
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.