Evidence map›Paper›PMID 23955275›Full record

ArticleNature biotechnology2013

Nature-inspired design of motif-specific antibody scaffolds.

James T Koerber, Nathan D Thomsen, Brett T Hannigan, William F Degrado, James A Wells

Abstract read
In one paragraph

Article in Nature biotechnology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing 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

42 citing papers in PubMed.

  1. Article
  2. Binding mode-guided development of high-performance antibodies targeting site-specific posttranslational modifications.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  3. Article
  4. Article
  5. Article
  6. Article
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  9. Review
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  11. Article
  12. Review
  13. Review
  14. Structural basis for differential recognition of phosphohistidine-containing peptides by 1-pHis and 3-pHis monoclonal antibodies.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  15. Synthesis and Evaluation of Non-Hydrolyzable Phospho-Lysine Peptide Mimics.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021
    Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

James T KoerberDepartment of Pharmaceutical Chemistry, University of California, San Francisco, California, USA.
Nathan D Thomsen
Brett T Hannigan
William F Degrado
James A Wells

Funding

Training Program in Computational GenomicsT32HG000046 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI JUNHYONG KIM, Mingyao Li · 1999 to 2026
$9.5M
De novo design of alpha-helical bundlesR37GM054616 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI DEGRADO, WILLIAM · 2004 to 2013
$3.6M
DE NOVO DESIGN OF ALPHA HELICAL BUNDLESR01GM054616 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI DEGRADO, WILLIAM · 1996 to 2016
$2.4M
Approaches to discover and quantify apoptotic biomarkers for cancer treatmentR01CA154802 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WELLS, JAMES A · 2011 to 2014
$1.3M
NCI NIH HHS R01 CA154802NHGRI NIH HHS T32 HG000046NIGMS NIH HHS GM54616NIGMS NIH HHS R01 GM054616NIGMS NIH HHS R37 GM054616
6 · The paper itself

Abstract

Aberrant changes in post-translational modifications (PTMs) such as phosphate groups underlie a majority of human diseases. However, detection and quantification of PTMs for diagnostic or biomarker applications often require PTM-specific monoclonal antibodies (mAbs), which are challenging to generate using traditional antibody-selection methods. Here we outline a general strategy for producing synthetic, PTM-specific mAbs by engineering a motif-specific 'hot spot' into an antibody scaffold. Inspired by a natural phosphate-binding motif, we designed and selected mAb scaffolds with hot spots specific for phosphoserine, phosphothreonine or phosphotyrosine. Crystal structures of the phospho-specific mAbs revealed two distinct modes of phosphoresidue recognition. Our data suggest that each hot spot functions independently of the surrounding scaffold, as phage display antibody libraries using these scaffolds yielded >50 phospho- and target-specific mAbs against 70% of target peptides. Our motif-specific scaffold strategy may provide a general solution for rapid, robust development of anti-PTM mAbs for signaling, diagnostic and therapeutic applications.

Indexed as

Protein EngineeringAmino Acid MotifsAmino Acid SequenceAntibodies, Phospho-SpecificAntibody SpecificityCrystallography, X-RayHumansModels, MolecularMolecular Sequence DataPhosphopeptidesSingle-Chain AntibodiesAntibodies, Phospho-SpecificPhosphopeptidesSingle-Chain Antibodies

Identifiers

PMID23955275
PMCPMC3795957

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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.