Evidence map›Paper›PMID 22964222›Full record

ArticleMolecular & cellular proteomics : MCP2012

Analysis of intact monoclonal antibody IgG1 by electron transfer dissociation Orbitrap FTMS.

Luca Fornelli, Eugen Damoc, Paul M Thomas, Neil L Kelleher, Konstantin Aizikov, Eduard Denisov, Alexander Makarov, Yury O Tsybin

Abstract read
In one paragraph

Article in Molecular & cellular proteomics : MCP, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing 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

58 citing papers in PubMed.

  1. Article
  2. Article
  3. Top-Down and Middle-Down Mass Spectrometry of Antibodies.Molecular & cellular proteomics : MCP · 2025
    Review
  4. Article
  5. Article
  6. Top-down proteomics.Nature reviews. Methods primers · 2024
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article
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

8 authors.

Luca FornelliBiomolecular Mass Spectrometry Laboratory, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Eugen Damoc
Paul M Thomas
Neil L Kelleher
Konstantin Aizikov
Eduard Denisov
Alexander Makarov
Yury O Tsybin

Funding

The UIUC Neuroproteomics Center on Cell-Cell SignalingP30DA018310 · NIDA · UNIVERSITY OF ILLINOIS URBANA-CHAMPAIGN · PI Elena V Romanova · 2004 to 2026
$24.9M
Eukaryotic Post-Translational ModificationsR01GM067193 · NIGMS · UNIVERSITY OF ILLINOIS URBANA-CHAMPAIGN · PI KELLEHER, NEIL L · 2003 to 2015
$4.0M
NIDA NIH HHS DA 018310NIDA NIH HHS P30 DA018310NIGMS NIH HHS GM 067193NIGMS NIH HHS R01 GM067193
6 · The paper itself

Abstract

The primary structural information of proteins employed as biotherapeutics is essential if one wishes to understand their structure-function relationship, as well as in the rational design of new therapeutics and for quality control. Given both the large size (around 150 kDa) and the structural complexity of intact immunoglobulin G (IgG), which includes a variable number of disulfide bridges, its extensive fragmentation and subsequent sequence determination by means of tandem mass spectrometry (MS) are challenging. Here, we applied electron transfer dissociation (ETD), implemented on a hybrid Orbitrap Fourier transform mass spectrometer (FTMS), to analyze a commercial recombinant IgG in a liquid chromatography (LC)-tandem mass spectrometry (MS/MS) top-down experiment. The lack of sensitivity typically observed during the top-down MS of large proteins was addressed by averaging time-domain transients recorded in different LC-MS/MS experiments before performing Fourier transform signal processing. The results demonstrate that an improved signal-to-noise ratio, along with the higher resolution and mass accuracy provided by Orbitrap FTMS (relative to previous applications of top-down ETD-based proteomics on IgG), is essential for comprehensive analysis. Specifically, ETD on Orbitrap FTMS produced about 33% sequence coverage of an intact IgG, signifying an almost 2-fold increase in IgG sequence coverage relative to prior ETD-based analysis of intact monoclonal antibodies of a similar subclass. These results suggest the potential application of the developed methodology to other classes of large proteins and biomolecules.

Indexed as

Amino Acid SequenceAntibodies, MonoclonalChromatography, LiquidFourier AnalysisHumansImmunoglobulin GMass SpectrometryMolecular Sequence DataPeptide FragmentsProteomicsSignal-To-Noise RatioStructure-Activity RelationshipAntibodies, MonoclonalImmunoglobulin GPeptide Fragments

Identifiers

PMID22964222
PMCPMC3518117

What OpenQuestion holds

Textmetadata
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.