Evidence map›Paper›PMID 24959685›Full record

ArticlePloS one2014

Structure-based prediction of asparagine and aspartate degradation sites in antibody variable regions.

Jasmin F Sydow, Florian Lipsmeier, Vincent Larraillet, Maximiliane Hilger, Bjoern Mautz, Michael Mølhøj, Jan Kuentzer, Stefan Klostermann, Juergen Schoch, Hans R Voelger and 4 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 6% 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

81 citing papers in PubMed, 1 synthesis or guideline pooled it, 154 citations in OpenAlex.

  1. Pooled it
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  15. DOTAD: A Database of Therapeutic Antibody Developability.Interdisciplinary sciences, computational life sciences · 2024
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21 more citing papers are in PubMed but not listed here.

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

14 authors at 2 institutions in 1 country.

Jasmin F SydowLarge Molecule Research, Roche Pharmaceutical Research and Early Development, Penzberg, Germany.
Florian LipsmeierTherapeutics Modalities Informatics, Roche Pharmaceutical Research and Early Development, Penzberg, Germany.
Vincent LarrailletLarge Molecule Research, Roche Pharmaceutical Research and Early Development, Penzberg, Germany.
Maximiliane HilgerLarge Molecule Research, Roche Pharmaceutical Research and Early Development, Penzberg, Germany.
Bjoern MautzLarge Molecule Research, Roche Pharmaceutical Research and Early Development, Penzberg, Germany.
Michael MølhøjLarge Molecule Research, Roche Pharmaceutical Research and Early Development, Penzberg, Germany.
Jan KuentzerDisease & Translational Informatics, Roche Pharmaceutical Research and Early Development, Penzberg, Germany.
Stefan KlostermannTherapeutics Modalities Informatics, Roche Pharmaceutical Research and Early Development, Penzberg, Germany.
Juergen SchochTherapeutics Modalities Informatics, Roche Pharmaceutical Research and Early Development, Penzberg, Germany.
Hans R VoelgerLarge Molecule Research, Roche Pharmaceutical Research and Early Development, Penzberg, Germany.
Joerg T RegulaLarge Molecule Research, Roche Pharmaceutical Research and Early Development, Penzberg, Germany.
Patrick CramerGene Center Munich and Department of Biochemistry, Center for Integrated Protein Science (CIPSM), Ludwig-Maximilians-Universität (LMU), Munich, Germany.
Apollon PapadimitriouPharmaceutical Sciences, Roche Pharmaceutical Research and Early Development, Penzberg, Germany.
Hubert KettenbergerLarge Molecule Research, Roche Pharmaceutical Research and Early Development, Penzberg, Germany.
Roche Pharma AG (Germany) · DECenter for Integrated Protein Science Munich · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Monoclonal antibodies (mAbs) and proteins containing antibody domains are the most prevalent class of biotherapeutics in diverse indication areas. Today, established techniques such as immunization or phage display allow for an efficient generation of new mAbs. Besides functional properties, the stability of future therapeutic mAbs is a key selection criterion which is essential for the development of a drug candidate into a marketed product. Therapeutic proteins may degrade via asparagine (Asn) deamidation and aspartate (Asp) isomerization, but the factors responsible for such degradation remain poorly understood. We studied the structural properties of a large, uniform dataset of Asn and Asp residues in the variable domains of antibodies. Their structural parameters were correlated with the degradation propensities measured by mass spectrometry. We show that degradation hotspots can be characterized by their conformational flexibility, the size of the C-terminally flanking amino acid residue, and secondary structural parameters. From these results we derive an accurate in silico prediction method for the degradation propensity of both Asn and Asp residues in the complementarity-determining regions (CDRs) of mAbs.

Indexed as

Structure-Activity RelationshipArtificial IntelligenceAsparagineAspartic AcidImmunoglobulin Variable RegionMetabolic Networks and PathwaysModels, MolecularMolecular ConformationProteolysisROC CurveAsparagineAspartic AcidImmunoglobulin Variable Region

Identifiers

PMID24959685
PMCPMC4069079
OpenAlexW2083857255

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.