Evidence map›Paper›PMID 32441507›Full record

ArticleAnalytical chemistry2020

Epitope and Paratope Mapping of PD-1/Nivolumab by Mass Spectrometry-Based Hydrogen-Deuterium Exchange, Cross-linking, and Molecular Docking.

Mengru Mira Zhang, Richard Y-C Huang, Brett R Beno, Ekaterina G Deyanova, Jing Li, Guodong Chen, Michael L Gross

Open access · greenAbstract read
In one paragraph

Article in Analytical chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
3.0field-weighted citation impact, top 7% 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

27 citing papers in PubMed, 54 citations in OpenAlex.

  1. Review
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  8. Review
  9. Peptide Antibodies: Current Status.Methods in molecular biology (Clifton, N.J.) · 2024
    Article
  10. Toward a MALDI in-source decay (ISD) method for top-down analysis of protein footprinting.European journal of mass spectrometry (Chichester, England) · 2023
    Article
  11. Article
  12. Article
  13. Article
  14. MALDI Peptide Mapping for Fast Analysis in Protein Footprinting.International journal of mass spectrometry · 2023
    Article
  15. Review
  16. Article
  17. Article
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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

7 authors at 2 institutions in 1 country.

Mengru Mira ZhangDepartment of Chemistry, Washington University, St. Louis, Missouri 63130, United States.ORCID 0000-0001-9082-1272
Richard Y-C HuangPharmaceutical Candidate Optimization, Nonclinical Research and Development, Bristol Myers Squibb Company, Princeton, New Jersey 08540, United States.ORCID 0000-0002-7172-110X
Brett R BenoMolecular Structure & Design, Small Molecule Drug Discovery, Bristol Myers Squibb Company, Princeton, New Jersey 08540, United States.
Ekaterina G DeyanovaPharmaceutical Candidate Optimization, Nonclinical Research and Development, Bristol Myers Squibb Company, Princeton, New Jersey 08540, United States.ORCID 0000-0002-9663-5590
Jing LiPharmaceutical Candidate Optimization, Nonclinical Research and Development, Bristol Myers Squibb Company, Princeton, New Jersey 08540, United States.
Guodong ChenPharmaceutical Candidate Optimization, Nonclinical Research and Development, Bristol Myers Squibb Company, Princeton, New Jersey 08540, United States.
Michael L GrossDepartment of Chemistry, Washington University, St. Louis, Missouri 63130, United States.ORCID 0000-0003-1159-4636
Bristol-Myers Squibb (United States) · USWashington University in St. Louis · US

Funding

TrainingP41GM103422 · NIGMS · WASHINGTON UNIVERSITY · PI YARASHESKI, KEVIN E · 2012 to 2019
$12.0M
A Biomedical Mass Spectrometry Resource: Ongoing Driving Biomedical ProjectsR24GM136766 · NIGMS · WASHINGTON UNIVERSITY · PI GROSS, MICHAEL L · 2020 to 2022
$2.3M
A MASS SPECTROMETER FOR PROTEIN FOOTPRINTINGS10OD016298 · OD · WASHINGTON UNIVERSITY · PI GROSS, MICHAEL L · 2014 to 2014
$450k
NIGMS NIH HHS P41 GM103422NIGMS NIH HHS R24 GM136766NIH HHS S10 OD016298
6 · The paper itself

Abstract

Programmed cell death-1 (PD-1), an antigen co-receptor on cell surfaces, is one of the conspicuous immune checkpoints. Nivolumab, a monoclonal antibody therapeutic approved by the FDA, binds to PD-1 and efficiently blocks its pathways. In this study, an integrated approach was developed to map the epitope/paratope of PD-1/nivolumab. The approach includes hydrogen-deuterium exchange mass spectrometry (HDX-MS) followed by electron-transfer dissociation (ETD), chemical cross-linking, and molecular docking. HDX-ETD offers some binding-site characterization with amino acid resolution. Chemical cross-linking provides complementary information on one additional epitope (i.e., the BC-loop) and a potential paratope at the N-terminus of the heavy chain. Furthermore, cross-linking identifies another loop region (i.e., the C'D-loop) that undergoes a remote conformational change. The distance restraints derived from the cross-links enable building high-confidence models of PD-1/nivolumab, evaluated with respect to a resolved crystal structure. This integrated strategy is an opportunity to characterize comprehensively other antigen-antibody interactions, to enable the understanding of binding mechanisms, and to design future antibody therapeutics.

Indexed as

Deuterium Exchange MeasurementAmino Acid SequenceAntigen-Antibody ComplexBinding SitesChromatography, High Pressure LiquidEpitope MappingEpitopesHumansMolecular Docking SimulationNivolumabProgrammed Cell Death 1 ReceptorProtein BindingProtein Structure, SecondaryTandem Mass SpectrometryAntigen-Antibody ComplexEpitopesNivolumabProgrammed Cell Death 1 Receptor

Identifiers

PMID32441507
PMCPMC7501946
OpenAlexW3027742687

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.