Evidence map›Paper›PMID 26399599›Full record

ArticleAnalytical chemistry2015

Investigating Therapeutic Protein Structure with Diethylpyrocarbonate Labeling and Mass Spectrometry.

Nicholas B Borotto, Yuping Zhou, Stephen R Hollingsworth, John E Hale, Eric M Graban, Robert C Vaughan, Richard W Vachet

Abstract read
In one paragraph

Article in Analytical chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing 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

28 citing papers in PubMed.

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  11. Cancer Conformational Landscape Shapes Tumorigenesis.Journal of proteome research · 2022
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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.

Nicholas B BorottoDepartment of Chemistry, University of Massachusetts , Amherst, Massachusetts 01003, United States.
Yuping ZhouDepartment of Chemistry, University of Massachusetts , Amherst, Massachusetts 01003, United States.
Stephen R HollingsworthDepartment of Molecular and Cellular Biochemistry, Indiana University , Bloomington, Indiana 47405, United States.
John E HaleQuarryBio , Bloomington, Indiana 47404, United States.
Eric M GrabanQuarryBio , Bloomington, Indiana 47404, United States.
Robert C VaughanDepartment of Molecular and Cellular Biochemistry, Indiana University , Bloomington, Indiana 47405, United States.
Richard W VachetDepartment of Chemistry, University of Massachusetts , Amherst, Massachusetts 01003, United States.

Funding

CHEMISTRY-BIOLOGY INTERFACE PREDOCTORAL TRAINING GRANTST32GM008515 · NIGMS · UNIVERSITY OF MASSACHUSETTS AMHERST · PI THOMPSON, LYNMARIE K. · 1995 to 2020
$4.3M
Acquisition of an Orbitrap MSS10OD010645 · OD · UNIVERSITY OF MASSACHUSETTS AMHERST · PI EYLES, STEPHEN J. · 2013 to 2013
$600k
NIGMS NIH HHS T32 GM008515NIH HHS S10 OD010645NIH HHS S10OD010645
6 · The paper itself

Abstract

Protein therapeutics are rapidly transforming the pharmaceutical industry. Unlike for small molecule therapeutics, current technologies are challenged to provide the rapid, high-resolution analyses of protein higher order structures needed to ensure drug efficacy and safety. Consequently, significant attention has turned to developing new methods that can quickly, accurately, and reproducibly characterize the three-dimensional structure of protein therapeutics. In this work, we describe a method that uses diethylpyrocarbonate (DEPC) labeling and mass spectrometry to detect three-dimensional structural changes in therapeutic proteins that have been exposed to degrading conditions. Using β2-microglobulin, immunoglobulin G1, and human growth hormone as model systems, we demonstrate that DEPC labeling can identify both specific protein regions that mediate aggregation and those regions that undergo more subtle structural changes upon mishandling of these proteins. Importantly, DEPC labeling is able to provide information for up to 30% of the surface residues in a given protein, thereby providing excellent structural resolution. Given the simplicity of the DEPC labeling chemistry and the relatively straightforward mass spectral analysis of DEPC-labeled proteins, we expect this method should be amenable to a wide range of protein therapeutics and their different formulations.

Indexed as

beta 2-MicroglobulinDiethyl PyrocarbonateGrowth HormoneHumansImmunoglobulin GMass SpectrometryModels, MolecularMolecular Structurebeta 2-MicroglobulinDiethyl PyrocarbonateGrowth HormoneImmunoglobulin G

Identifiers

PMID26399599
PMCPMC4939621

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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.