Evidence map›Paper›PMID 40533519›Full record

ArticleCommunications biology2025

Optimised nanobody-based quenchbodies for enhanced protein detection.

Jordan H Cater, Nehad S El Salamouni, Ghada H Mansour, Sebastian Hutchinson, Conall Mc Guinness, Stefan H Mueller, Richard R Spinks, Nirukshan Shanmugam, Adeline Pichard-Kostuch, Viktor Zahoransky and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

16 authors.

Jordan H CaterMolecular Horizons, School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW, 2522, Australia.ORCID http://orcid.org/0000-0003-3608-929X
Nehad S El Salamouni *Molecular Horizons, School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW, 2522, Australia.ORCID http://orcid.org/0000-0001-6856-6332
Ghada H Mansour *Laboratoire de Biochimie, Chimie Biologie et Innovation, ESPCI Paris, Université PSL, Paris, France.ORCID http://orcid.org/0000-0001-8316-2619
Sebastian Hutchinson *Laboratoire de Biochimie, Chimie Biologie et Innovation, ESPCI Paris, Université PSL, Paris, France.
Conall Mc GuinnessMolecular Horizons, School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW, 2522, Australia.ORCID http://orcid.org/0000-0002-9733-6699
Stefan H MuellerMolecular Horizons, School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW, 2522, Australia.ORCID http://orcid.org/0000-0002-0930-2000
Richard R SpinksMolecular Horizons, School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW, 2522, Australia.
Nirukshan ShanmugamMolecular Horizons, School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW, 2522, Australia.
Adeline Pichard-KostuchLaboratoire de Biochimie, Chimie Biologie et Innovation, ESPCI Paris, Université PSL, Paris, France.ORCID http://orcid.org/0000-0001-9220-8535
Viktor ZahoranskyLaboratoire de Biochimie, Chimie Biologie et Innovation, ESPCI Paris, Université PSL, Paris, France.
Harshad GhodkeMolecular Horizons, School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW, 2522, Australia.
Marco Ribezzi-CrivellariLaboratoire de Biochimie, Chimie Biologie et Innovation, ESPCI Paris, Université PSL, Paris, France.
Haibo YuMolecular Horizons, School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW, 2522, Australia.ORCID http://orcid.org/0000-0002-1099-2803
Antoine M van OijenMolecular Horizons, School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW, 2522, Australia. vanoijen@uow.edu.au.ORCID http://orcid.org/0000-0002-1794-5161
Andrew D GriffithsLaboratoire de Biochimie, Chimie Biologie et Innovation, ESPCI Paris, Université PSL, Paris, France. andrew.griffiths@espci.fr.ORCID http://orcid.org/0000-0002-0808-3539
Lisanne M SpenkelinkMolecular Horizons, School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW, 2522, Australia. lisanne@uow.edu.au.ORCID http://orcid.org/0000-0002-5511-8757

Funding

Department of Health | National Health and Medical Research Council (NHMRC) 2007778
6 · The paper itself

Abstract

Quenchbodies, antibodies labelled with fluorophores that increase in intensity upon antigen binding, offer great promise for biosensor development. Nanobody-based quenchbodies are particularly attractive due to their small size, ease of expression, high stability, rapid evolvability, and amenability to protein engineering. However, existing designs for protein detection show limited dynamic range, with fluorescence increases of only 1.1-1.4 fold. Here we identify the tryptophan residues in the nanobody complementarity-determining regions (CDRs) that are critical to quenchbody performance. Using a combination of rational design and molecular dynamics simulations, we developed an optimised nanobody scaffold with tryptophans introduced at key positions. We used this scaffold in an in vitro directed-evolution screen against human inflammatory cytokine interleukin-6 (IL-6). This yielded quenchbodies with 1.5-2.4-fold fluorescence increases, enabling IL-6 detection down to 1-2 nM. Our scaffold provides a valuable platform for developing biosensors for diverse protein targets, with applications in research, diagnostics, and environmental monitoring.

Indexed as

Biosensing TechniquesInterleukin-6Single-Domain AntibodiesComplementarity Determining RegionsFluorescent DyesHumansMolecular Dynamics SimulationComplementarity Determining RegionsFluorescent DyesIL6 protein, humanInterleukin-6Single-Domain Antibodies

Identifiers

PMID40533519
PMCPMC12177037

What Socratic 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 Socratic graph.