Evidence map›Paper›PMID 28901129›Full record

ArticleAnalytical chemistry2017

Peptide-Level Interactions between Proteins and Small-Molecule Drug Candidates by Two Hydrogen-Deuterium Exchange MS-Based Methods: The Example of Apolipoprotein E3.

Hanliu Wang, Don L Rempel, Daryl Giblin, Carl Frieden, Michael L Gross

Abstract read
In one paragraph

Article in Analytical chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Hydrogen-Deuterium Exchange Mass Spectrometry for Molecular Glue Characterization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
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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.

Hanliu WangDepartment of Chemistry, Washington University in St. Louis , One Brookings Drive, St. Louis, Missouri 63130, United States.
Don L RempelDepartment of Chemistry, Washington University in St. Louis , One Brookings Drive, St. Louis, Missouri 63130, United States.
Daryl GiblinDepartment of Chemistry, Washington University in St. Louis , One Brookings Drive, St. Louis, Missouri 63130, United States.
Carl FriedenDepartment of Biochemistry and Molecular Biophysics, School of Medicine, Washington University in St. Louis , 660 South Euclid Avenue, St. Louis, Missouri 63110, United States.
Michael L GrossDepartment of Chemistry, Washington University in St. Louis , One Brookings Drive, St. Louis, Missouri 63130, United States.ORCID 0000-0003-1159-4636

Funding

TrainingP41GM103422 · NIGMS · WASHINGTON UNIVERSITY · PI YARASHESKI, KEVIN E · 2012 to 2019
$12.0M
ALZHEIMER'S DISEASE: DEFINING THE APOE-AMYLOID-BETA INTERACTIONRF1AG044331 · NIA · WASHINGTON UNIVERSITY · PI FRIEDEN, CARL · 2014 to 2014
$1.6M
NIA NIH HHS RF1 AG044331NIGMS NIH HHS P41 GM103422
6 · The paper itself

Abstract

We describe a platform utilizing two methods based on hydrogen-deuterium exchange (HDX) coupled with mass spectrometry (MS) to characterize interactions between a protein and a small-molecule ligand. The model system is apolipoprotein E3 (apoE3) and a small-molecule drug candidate. We extended PLIMSTEX (protein-ligand interactions by mass spectrometry, titration, and H/D exchange) to the regional level by incorporating enzymatic digestion to acquire binding information for peptides. In a single experiment, we not only identified putative binding sites, but also obtained affinities of 6.0, 6.8, and 10.6 μM for the three different regions, giving an overall binding affinity of 7.4 μM. These values agree well with literature values determined by accepted methods. Unlike those methods, PLIMSTEX provides site-specific binding information. The second approach, modified SUPREX (stability of unpurified proteins from rates of H/D exchange) coupled with electrospray ionization (ESI), allowed us to obtain detailed understanding about apoE unfolding and its changes upon ligand binding. Three binding regions, along with an additional site, which may be important for lipid binding, show increased stability (less unfolding) upon ligand binding. By employing a single parameter, ΔC

Indexed as

Apolipoprotein E3Binding SitesDeuteriumDeuterium Exchange MeasurementLigandsMonte Carlo MethodPeptidesProtein BindingProtein UnfoldingSmall Molecule LibrariesSpectrometry, Mass, Electrospray IonizationApolipoprotein E3DeuteriumLigandsPeptidesSmall Molecule Libraries

Identifiers

PMID28901129
PMCPMC5655995

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Registered trials

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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.