Evidence map›Paper›PMID 26007606›Full record

ArticleMethods (San Diego, Calif.)2016

ESI-IMS-MS: A method for rapid analysis of protein aggregation and its inhibition by small molecules.

Lydia M Young, Janet C Saunders, Rachel A Mahood, Charlotte H Revill, Richard J Foster, Alison E Ashcroft, Sheena E Radford

Abstract read
In one paragraph

Article in Methods (San Diego, Calif.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
–field-weighted citation impact
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

22 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Helical sulfonyl-γ-AApeptides modulating Aβ oligomerization and cytotoxicity by recognizing Aβ helix.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Wanted: more monitoring and control during inclusion body processing.World journal of microbiology & biotechnology · 2018
    Review
  18. Article
  19. Article
  20. Small molecule probes of protein aggregation.Current opinion in chemical biology · 2017
    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.

Lydia M YoungAstbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom; School of Molecular and Cellular Biology, University of Leeds, LS2 9JT, United Kingdom. Electronic address: bs08lw@leeds.ac.uk.
Janet C SaundersAstbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom; School of Molecular and Cellular Biology, University of Leeds, LS2 9JT, United Kingdom. Electronic address: bsjct@leeds.ac.uk.
Rachel A MahoodAstbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom; School of Molecular and Cellular Biology, University of Leeds, LS2 9JT, United Kingdom. Electronic address: bs08ram@leeds.ac.uk.
Charlotte H RevillAstbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom; School of Chemistry, University of Leeds, LS2 9JT, United Kingdom. Electronic address: C.H.Revill@leeds.ac.uk.
Richard J FosterAstbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom; School of Chemistry, University of Leeds, LS2 9JT, United Kingdom. Electronic address: R.Foster@leeds.ac.uk.
Alison E AshcroftAstbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom; School of Molecular and Cellular Biology, University of Leeds, LS2 9JT, United Kingdom. Electronic address: A.E.Ashcroft@leeds.ac.uk.
Sheena E RadfordAstbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom; School of Molecular and Cellular Biology, University of Leeds, LS2 9JT, United Kingdom. Electronic address: S.E.Radford@leeds.ac.uk.

Funding

Biotechnology and Biological Sciences Research Council BB/E012558/1Biotechnology and Biological Sciences Research Council BB/F01614X/1Biotechnology and Biological Sciences Research Council BB/H014713/1Biotechnology and Biological Sciences Research Council BB/I015361/1European Research Council 322408
6 · The paper itself

Abstract

Electrospray ionisation-ion mobility spectrometry-mass spectrometry (ESI-IMS-MS) is a powerful method for the study of conformational changes in protein complexes, including oligomeric species populated during protein self-aggregation into amyloid fibrils. Information on the mass, stability, cross-sectional area and ligand binding capability of each transiently populated intermediate, present in the heterogeneous mixture of assembling species, can be determined individually in a single experiment in real-time. Determining the structural characterisation of oligomeric species and alterations in self-assembly pathways observed in the presence of small molecule inhibitors is of great importance, given the urgent demand for effective therapeutics. Recent studies have demonstrated the capability of ESI-IMS-MS to identify small molecule modulators of amyloid assembly and to determine the mechanism by which they interact (positive, negative, non-specific binding, or colloidal) in a high-throughput format. Here, we demonstrate these advances using self-assembly of Aβ40 as an example, and reveal two new inhibitors of Aβ40 fibrillation.

Indexed as

Amyloid beta-PeptidesHigh-Throughput Screening AssaysHumansHydrogen-Ion ConcentrationLigandsModels, MolecularPeptide FragmentsProtein AggregatesProtein BindingProtein ConformationSmall Molecule LibrariesSolutionsSpectrometry, Mass, Electrospray IonizationAmyloid beta-Peptidesamyloid beta-protein (1-40)LigandsPeptide FragmentsProtein AggregatesSmall Molecule LibrariesSolutionsAmyloidAβESI-IMS–MSLigand screeningSmall molecule inhibitor

Identifiers

PMID26007606
PMCPMC4769093

What OpenQuestion holds

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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.