Evidence map›Paper›PMID 27974464›Full record

ArticleThe Journal of biological chemistry2017

Affinity Maturation of a Cyclic Peptide Handle for Therapeutic Antibodies Using Deep Mutational Scanning.

Martijn van Rosmalen, Brian M G Janssen, Natalie M Hendrikse, Ardjan J van der Linden, Pascal A Pieters, Dave Wanders, Tom F A de Greef, Maarten Merkx

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

18 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Genetically EncodedACS synthetic biology · 2025
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  9. Article
  10. Review
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  12. A Genetically Encoded, Phage-Displayed Cyclic-Peptide Library.Angewandte Chemie (International ed. in English) · 2019
    Review
  13. Review
  14. Article
  15. Nonproteinogenic deep mutational scanning of linear and cyclic peptides.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  16. Article
  17. Article
  18. 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 at 1 institution in 1 country.

Martijn van RosmalenFrom the Laboratory of Chemical Biology and Institute for Complex Molecular Systems (ICMS), Department of Biomedical Engineering, Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands.
Brian M G JanssenFrom the Laboratory of Chemical Biology and Institute for Complex Molecular Systems (ICMS), Department of Biomedical Engineering, Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands.
Natalie M HendrikseFrom the Laboratory of Chemical Biology and Institute for Complex Molecular Systems (ICMS), Department of Biomedical Engineering, Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands.
Ardjan J van der LindenFrom the Laboratory of Chemical Biology and Institute for Complex Molecular Systems (ICMS), Department of Biomedical Engineering, Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands.
Pascal A PietersFrom the Laboratory of Chemical Biology and Institute for Complex Molecular Systems (ICMS), Department of Biomedical Engineering, Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands.
Dave WandersFrom the Laboratory of Chemical Biology and Institute for Complex Molecular Systems (ICMS), Department of Biomedical Engineering, Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands.
Tom F A de GreefFrom the Laboratory of Chemical Biology and Institute for Complex Molecular Systems (ICMS), Department of Biomedical Engineering, Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands.
Maarten MerkxFrom the Laboratory of Chemical Biology and Institute for Complex Molecular Systems (ICMS), Department of Biomedical Engineering, Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands m.merkx@tue.nl.
Eindhoven University of Technology · NL

Funding

European Research Council 280255
6 · The paper itself

Abstract

Meditopes are cyclic peptides that bind in a specific pocket in the antigen-binding fragment of a therapeutic antibody such as cetuximab. Provided their moderate affinity can be enhanced, meditope peptides could be used as specific non-covalent and paratope-independent handles in targeted drug delivery, molecular imaging, and therapeutic drug monitoring. Here we show that the affinity of a recently reported meditope for cetuximab can be substantially enhanced using a combination of yeast display and deep mutational scanning. Deep sequencing was used to construct a fitness landscape of this protein-peptide interaction, and four mutations were identified that together improved the affinity for cetuximab 10-fold to 15 nm Importantly, the increased affinity translated into enhanced cetuximab-mediated recruitment to EGF receptor-overexpressing cancer cells. Although in silico Rosetta simulations correctly identified positions that were tolerant to mutation, modeling did not accurately predict the affinity-enhancing mutations. The experimental approach reported here should be generally applicable and could be used to develop meditope peptides with low nanomolar affinity for other therapeutic antibodies.

Indexed as

Cell Line, TumorCetuximabErbB ReceptorsHumansPeptides, CyclicSaccharomyces cerevisiaeCetuximabEGFR protein, humanErbB ReceptorsPeptides, Cyclicantibodycyclic peptidedirected evolutionepidermal growth factor receptor (EGFR)protein engineering

Identifiers

PMID27974464
PMCPMC5270489
OpenAlexW2573068944

What OpenQuestion holds

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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.